The in vitro activity of pazufloxacin (PZFX), a new fluoroquinolone, was compared with those of ofloxacin (OFLX), norfloxacin (NFLX), ciprofloxacin (CPFX) and levofloxacin (LVFX). The MIC₉₀ of PZFX against methicillin-susceptible and methicillin-resistant _{Staphylococcus aureus} were 0.39 and 12.5μg/ml, better than those of the other reference fluoroquinolones. Some isolates of CPFX-resistant S. aureus (MIC of CPFX, ≥3.13μg/ml) were still susceptible to PZFX (MIC of PZFX, ≤0.39μg/ml). The MIC₉₀s of PZFX against Enterobacteriaceae (except Serratia marcescens) were 0.024 to 0.39μg/ml, and against S. marcescens and Pseudomonas aeruginosa were 6.25 and 3.13μg/ml, which they were comparable to CPFX and better than those of the other reference quinolones. The activity of PZFX against anaerobes was comparable to those of CPFX and LVFX, and better than those of OFLX and NFLX. The MBCs of PZFX were either equal to or two-fold higher than the MICs. At a concentration of four times the MIC, the frequencies of appearance of spontaneous mutants resistant to PZFX against S. aureus, Escherichia coli, S. marcescens and P. aeruginosa were 2.3 × 10^-8 to < 1.2 ×10^-9 The 50% inhibitory concentrations of PZFX for DNA gyrases isolated from S. aureus, E. coli and P. aeruginosa were 32, 0.88 and 14μg/ml, respectively.
PZFX had a broad spectrum of activity and had potent activity against Gram-positive and-negative bacteria. Its activity was bactericidal, and its mechanism of action was the inhibition of the supercoiling activity of bacterial DNA gyrase.

View full abstract

Pazufloxacin (PZFX) is a novel quinolone useful orally and parenterally. In the study described here, the in vitro activities of PZFX were compared with those of ofloxacin (OFLX), norfloxacin (NFLX), ciprofloxacin, tosufloxacin (TFLX) and sparfloxacin (SPFX). MIC₉₀s of PZFX against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA; 47 strains), high-level resistant MRSA (64 strains), CNS (41 strains), Streptococcus pneumoniae (18strains), Streptococcus pyogenes (48 strains), Enterococcus faecalis (37 strains), Enterococcus faecium (41 strains), Escherichia coli CS2 (R+)(43 strains), Klebsiella pneumoniae (47 strains), Proteus mirabilis (48 strains), Proteus vulgaris (54 strains), Providencia rettgeri (47 strains), Morganella morganii (49 strains), Serratia marcescens (50 strains), Enterobacter cloacae (50 strains), Citrobacter freundii (50 strains), Pseudomonas aeruginosa (50 strains), Acinetobacter calcoaceticus (41 strains), Xanthomonas maltophilia (48 strains), Pseudomonas cepacia (33 strains), Haemophilus influenzae (11 strains) and Bacteroides fragilis (38 strains) were 0.39, 3.13, 0.39, 3.13, 3.13, 3.13, 6.25, 0.2, 0.1, 0.025, 0.025, 6.25, 0.2, 1.56, 0.78, 0.78, 12.5, 3.13, 0.78, 1.56, ≤0.013, and 6.25μg/ml, respectively. PZFX showed superior activity against gram-negative bacteria to other tested quinolones. The in vitro activity of PZFX against gram-positive bacteria was comparable to 2-to 32-fold greater than those of OFLX and NFLX, and 2-to 8-fold less than those of TFLX and SPFX. PZFX had an apparent synergy of bactericidal effect on E. coli cells with cultured mouse macrophages. IC₅₀s of PZFX against HeLa, CHO-K1, and IMR-32 cells were higher than 100μg/ml, greater than those of OFLX and other new quinolones. PZFX had high selective toxicity against various bacteria but not mammalian cells.

View full abstract

The in vitro and in vivo antibacterial activities of pazufloxacin (PZFX) were compared with those of ciprofloxacin (CPFX), ofloxacin (OFLX), sparfloxacin (SPFX) and tosufloxacin (TFLX).
PZFX showed strong antibacterial activity next to those of SPFX and TFLX against the genus Staphylococcus, including methicillin-resistant Staphylococcus aureus, and its antibacterial activity against the genus Streptococcus was almost equal to those of CPFX and OFLX. Against members of the family Enterobacteriaceae, except for Proteus rettgeri, the MIC₉₀ of PZFX was less than 4μg/ml, a level of activity which was the same as or higher than that of CPFX. For glucose-nonfermentative gram-negative rods, the activity of PZFX was the same as that of CPFX.
As for the influence on the growth curve of Pseudomonas aeruginosa, PZFX showed a strong antibacterial effect within a short time. In addition, PZFX suppressed regrowth 3 hours longer than OFLX in an in vitro pharmacokinetic model which reproduced the changes in human serum concentration.
In systemic infection caused by two strains of Staphylococcus aureus and two of gram-negative rods in mice, the ED₅₀s of PZFX was 0.01-0.32mg/mouse. The therapeutic effects were superior to those of other drugs tested except for SPFX on 2 strains of S. aureus and Klebsiella pneumoniae 3K-25 infection and CPFX on Pseudomonas aeruginosa E7 infection. In respiratory infection caused byK. pneumoniae 3 K-25 and pyelonephritic infection caused by Escherichia coli TMS3 in mice, the therapeutic effects of PZFX were superior to those of other drugs except for SPFX. In P. aeruginosa KU-1 pyelonephritic infection mice, the therapeutic effect of PZFX was most active among the drugs tested.
In a pharmacokinetic study using mice, PZFX rapidly reached the maximum concentration in serum, lung and kidney with the peak values higher than those of control drugs (CPFX, OFLX, SPFX and TFLX). The half-lives of PZFX in serum, lung and kidney were almost equal to those of OFLX.

View full abstract

The in vitro and in vivo postantibiotic effects (PAEs) of pazufloxacin (PZFX), a new synthetic antimicrobial agent, were compared with those of ofloxacin (OFLX). After 1-hour exposure of Staphylococcus aureus Smith to 2 MICs of PZFX and OFLX, the in vitro PAEs were 1.75 and 1.95 hours, respectively. Similarly, the in vitro PAEs of PZFX and OFLX against Klebsiella pneumoniae BK were 1.35 and 0.85 hours, respectively. The PAEs of PZFX and OFLX at 4 MICs were 2.08 and 1.95 hours, respectively. Higher drug concentrations prolonged the PAEs.
PZFX was subcutaneously injected, at a dose of 4 mg/kg of body weight, to the back of mice infected with K. pneumoniae BK. The in vivo PAE and the maximum bactericidal activity (ΔLog₁₀ CFU/Thigh) of PZFX were 2.2 hours and 2.24, respectively, slightly superior to the 1.2 hours and 1.67, respectively, of OFLX.

View full abstract

The antimicrobial activity of pazufloxacin (PZFX), a new quinolone, was determined against 769 recent clinical isolates and compared with those of norfloxacin, ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, fleroxacin and sparfloxacin. PZFX showed superior antimicrobial activity against the species of Streptococcus and Enterococcus, and the MICs90 of PZFX against methicillin-sensitive and methicillinresistant Staphylococcus aureus were 0.2 and 12.5μg/ml, respectively. The MICs of PZFX against most species of Enterobacteriaceae were less than 3.13μg/ml. PZFX showed the equal or the highest antimicrobial activity against the species of Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Proteus mirabilis, Morganella morganii and Serratia marcescens among the agents tested.
Resistance to PZFX was induced in stepwise fashion in broth cultures of S. aureus, E. coli and Pseudomonas aeruginosa strains, indicating that the rate was very slow, and the increased level of resistance did not exceed fourfold.
The in vitro postantibiotic effect (PAE) of PZFX was evaluated. When strains of E. coli, Klebsiella pneumoniae and P. aeruginosa were exposed to PZFX at 2 MICs for 2 hours, the durations of PAE were 1.3, 1.6 and 1.7 hours, respectively, and PZFX tended to show a slightly shorter duration of PAE than the reference quinolones.
Although PZFX alone had no bactericidal activity against the sessile cells of the P. aeruginosa strain tested, PZFX showed synergistic bactericidal activity when combined with sub-MICs of erythromycin or clarithromycin.

View full abstract

The in vitro activity of pazufloxacin (PZFX), a new quinolone, was compared with those of tosufloxacin (TFLX), ciprofloxacin (CPFX), ofloxacin (OFLX) and norfloxacin (NFLX) against a variety of anaerobic bacteria and small number of facultative anaerobic bacteria.
PZFX had broad spectrum against gram-positive and gram-negative reference strains of anaerobes, inhibiting many anaerobic bacterial strains at 3.13μg/ml or less. However, PZFX showed weak activity against some ofPeptostreptococcus spp. and Clostridium spp., and Bacteroides fragilis group organisms. No influence of inoculum size upon antimicrobial activity was seen in PZFX. In the study against fresh clinical isotes, generally PZFX was less active than TFLX, as active as CPFX and OFLX, and more active than NFLX. PZFX was as active against imipenem-resistant B. fragilis group organisms as against imipenem-sensitive B. fragilis group organisms but not active against OFLX-resistant B. fragilis. These results suggested that PZFX treatment may be effective against infections with many of Peptostreptococcus spp., Prevotella spp. and Porphyromonas spp., and some of Clostridium spp. but not B. fragilis group organisms and Prevotella bivia.

View full abstract

The in vitro and in vivo antimicrobial activities of pazufloxacin (PZFX), a new synthetic antimicrobial agent, were studied and compared with those of reference agents, such as ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX) and sparfloxacin (SPFX). PZFX showed a broad in vitro antibacterial spectrum against both gram-negative and gram-positive organisms, showing 2-4 times higher antimicrobial activity than OFLX and equal to or slightly higher than that of CPFX. The antibacterial activity of PZFX was not influenced with inoculum size, but it was reduced slightly with addition of horse serum. As the control drugs, PZFX showed dose-dependent bactericidal activity.
In experimental systemic infections in mice, the therapeutic effect of PZFX against methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes was less than that of TFLX and SPFX, but higher than that of OFLX and CPFX. PZFX showed the highest therapeutic effect of the drugs examined against methicillin-resistant S. aureus and gram-negative organisms including Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa.
To determine their levels in blood, 10mg/kg of individual drugs were orally administered to mice. The maximum serum level (Cmax) of PZFX, 2.76μg/ml, was the highest among the drugs examined, however, its half-life in blood (T_1/2), 29.8 min, was the shortest.

View full abstract

It is well known that bacteria that form a biofilm are strongly resistant to many antimicrobial agents. Prior to biofilm formation, i.e., during adherance to the solid phase, bacteria also show resistance to the bactericidal activity of antimicrobial agents. In evaluating antimicrobial agents, their antibacterial activity against adherent bacteria should also be determined. The antibacterial activity of a newly developed quinolone antimicrobial agent, pazufloxacin (PZFX), against bacteria adhering to the solid phase was determined and compared with that of ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX).
PZFX showed a significantly low MIC for adherent Staphylococcus aureus (MICAD) and MBC for adherent S. aureus (MIC^AD). Against Staphylococcus epidermidis, the MICAD and MIC^AD of PZFX were equal or superior to those of CPFX and OFLX, whereas, inferior to those of TFLX. PZFX showed lower MIC^AD for Pseudomonas aeruginosa than CPFX and OFLX, whereas the MICAD of PZFX was inferior to that of CPFX. Against Escherichia coli, the MIC^AD and MIC^AD of PZFX were equal to those of TFLX, but the MIC^AD of PZFX was superior to that of CPFX and OFLX.
These results suggest that PZFX is an effective quinolone preparation for adherent bacteria.

View full abstract

We compared the in vitro and in vivo antibacterial activity of pazufloxacin (PZFX) with those of other new quinolones.
The results are summerized as follows:
1) PZFX exhibited a broad spectrum with potent antibacterial activity against Gram-positive bacteria, Gram-negative bacteria including Pseudomonas aeruginosa and anaerobic bacteria.
2) The antibacterial activity of PZFX was superior to that of ofloxacin (OFLX) against Staphylococcus aureus including methicillin-resistant S. aureus. Against Escherichia coli, Salmonella enteritidis, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Haemophilus influenzae and Legionella sp., the MIC₉₀ of PZFX were below 0.05μg/ml. The activities of PZFX against Gram-negative bacteria were superior to those of OFLX.
3) The antibacterial activity of PZFX was decreased by Ca²⁺, Mg²⁺, but its activity was unaffected by the type of culture medium, inoculum size or addition of human serum except for medium pH.
4) PZFX exhibited potent bactericidal action against various bacteria at the concentration above the MIC.
5) PZFX changed the morphology of E. coli KL-16 to filamentous shape (1/4 MIC), and caused abnormal cell division (1 MIC)
6) The appearance rate of spontaneous resistant mutants by PZFX was very low.
7) PZFX was strongly inhibited the supercoiling activity of DNA gyrase purified from E. coli and others. On the other hand, the inhibitory effect of PZFX against mammalian topoisomerase II from calf thymus was more weaker than those of OFLX or ciprofloxacin (CPFX)
8) The therapeutic effects of PZFX against mouse systemic infection were c.a. 2-8 fold superior to those of OFLX. Against mouse experimental respiratory tract infection and urinary tract infection, PZFX were also superior to those of OFLX, CPFX.

View full abstract

The short term bactericidal activity and the in vitro postantibiotic effect (PAE) of pazufloxacin (PZFX) against Pscudomonas acruginosa, Eschcrichia coli and methicillin-resistant Staphylococcus aureus (MRSA) were compared with those of ofloxacin (OFLX) and ciprofloxacin (CPFX).
1) For the studies of short term bactericidal activities, viable cell counts were determined until 4h at concentrations which approximated the human serum levels after oral administration of 200 mg. The bacterial killing for P. acruginosa and E. coli were seen by 0.25h, and viable cell counts of P. aeruginosa decreased more rapidly than E. coli in all three drugs. The bacterial killing for MRSA was most slowly. The bactericidal activity of PZFX was superior to that of OFLX and was the same as that of CPFX against P. acruginosa and E. coli, and superior to that of OFLX and CPFX against MRSA, when the drug concentrations were equal.
2) Upon an exposure to 8 NIIC for 0.5h, the PAEs of PZFX, OFLX and CPFX against P. aeriiginosa were -1.2h, 3.1h and 2.8h, against E. coli were 2.2h, 1.9h and 1.5h and against MRSA were 1.7h, 2.0h and 1.2h, respectively. Upon an exposure to 2 NIIC for 2h, the PAEs of PZFX, OFLX and CPFX against P. acruginosa wore 1.1h, 0.3h and 0.3h, against E. coli were 1.5h, 1.411 and 1.3h and against MRSA were 1.5h, 1.6h and 1.2h, respectively. The exposure to high level for short time produced longer PAEs in E. coli and P. aeruginosa.

View full abstract

The bactericidal activity of pazufloxacin (PZFX) against Pseudomonas aeruginosa using the simulation model at 200mg oral dose was compared with those of ofloxacin (OFLX, 200mg p.o.) and sparfloxacin (SPFX, 300mg p.o.).
PZFX showed the most rapid bactericidal effect, with a more than 2 log reduction of the bacterial counts within 0.5h. The bactericidal effect of OFLX occured at 1h after dosing. The maximum reduction of bacterial counts was more than 4 log in PZFX and 2.1 log-3 log in OFLX. SPFX only showed the bacteriostatic effect within 10h after dosing.
The susceptibilities of colonies recovered at 24h following exposure to drugs in simulation model and drug-free control were determined. The susceptibilities of colonies exposed to PZFX were same as that of control. In contrast, OFLX and SPFX selected the drug-resistant colonies.
We examined the significance of the pharmacokinetic character of PZFX on bactericidal effect and emergence of resistance using PZFX in the model simulating serum level of OFLX, because the peak concentration of OFLX was lower than that of PZFX and the half-life of OFLX was longer than that of PZFX. The effect of inhibition on regrowth of PZFX in the model simulating serum level of OFLX was superior to that of PZFX in the model simulating serum level of PZFX. However, the emergence of resistance was occured using the model simulating serum level of OFLX.
These data suggest that the pharmacokinetic character of PZFX have influence on its rapid bactericidal effect and prevent the emergence of resistance.

View full abstract

The in vitro and in vivo antibacterial activities of pazufloxacin (PZFX) against streptococci were compared with those of quinolones and -cephems.
The antibacterial activity of PZFX against Streptococcus pneumoniae isolated from clinical materials was inferior to tosufloxacin (TFLX) and ciprofloxacin (CPFX), similar to ofloxacin (OFLX), and superior to norfloxacin (NFLX) and fleroxacin (FLRX). Against penicillin susceptible S. pneumoniae, it was inferior to cefaclor (CCL). Against penicillin insensitive and resistant S. pneumoniae, it was superior to CCL. The antibacterial activities of PZFX against Streptococcus pyogenes and Streptococcus agalactiae were inferior to those of TFLX, CPFX and OFLX, and superior to those of NFLX and FLRX.
The bactericidal activities of PZFX against penicillin susceptible and resistant S. pneumoniae were similar to other quinolones, which depended on drug concentration.
The therapeutic effects of PZFX on systemic infection and experimental pneumonia in mice caused by penicillin susceptible and resistant S. pneumoniae were inferior to those of TFLX, but similar to those of OFLX. The therapeutic effects of PZFX against these infections caused by penicillin resistant S. pneumoniae were superior to those of cefixime. These results reflected approximately the MICs of each antimicrobial agents.

View full abstract

In order to examine the transfer of quinolones to inflammation focus, the concentrations of pazufloxacin (PZFX), ofloxacin (OFLX) and ciprofloxacin (CPFX) were measured using subcutaneous disk model, tissue cage model and CMC pouch model. In disk implanted model, the concentration of PZFX in disk was nearly proportional to the serum concentration. Although the half life of PZFX in transdate was shorter than that of OFLX, the Cmax of PZFX at the focus was higher than that of OFLX. In tissue cage model and CMC pouch model, the exudate levels of PZFX were higher than those of OFLX and CPFX. The therapeutic effects of PZFX against the single infection with Pseudomonas aeruginosa and mix infection with P. aeruginosa and Staphylococcus aureus at inflammation focus were superior to those of OFLX and CPFX because of its potent antibacterial activities and high concentrations in the focus.

View full abstract

The penetration of a new quinolone, pazufloxacin (PZFX), was compared with those of ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX) using human polymorphonuclear leukocyte (PMN) and various human tissue culture cells (Intestine 407, MRC-5 and Chang Liver). The intracellular bactericidal activities against Pseudomonas aeruginosa S-1299 in human PMN, and Salmonella enteritidis C-32 in human Intestine 407 cells were also compared.
The cellular concentration to the extracellular concentration (C/E ratio) of PZFX in human PMN was similar to that of OFLX but lower than those of CPFX and TFLX. The penetration of PZFX into human tissue culture cells was also lower than those of other three quinolones.
The intracellular bactericidal activity of PZFX against P. aeruginosa S-1299 phagocyted by human PMN was somewhat superior to that of OFLX, and equal to those of CPFX and TFLX, and its activity against S. enteritidis C-32 infected in human Intestine 407 cells was inferior to that of TFLX, but equal to those of OFLX and CPFX.
It is concluded that the penetration of PZFX into human cells was somewhat lower than those of other three quinolones, but intracellular bactericidal activity of PZFX was equal to those of other quinolones.

View full abstract

1. Minimum inhibitory concentrations (MICs)(inoculum size 10⁴ CFU/well) of pazufloxacin (PZFX), ofloxacin (OFLX), and tosufloxacin (TFLX) were determined against 62 isolates of Staphylococcus aureus from skin and skin structure infections. PZFX showed a peak of MIC distribution at 1μg/ml (34 isolates), OFLX at 1μg/ml (28 isolates), and TFLX at 0.06μg/ml (32 isolates).
2. Serum and skin concentrations of PZFX after a single oral administration of PZFX (20 mg/kg) were determined in rats. Mean serum concentrations were 2.34, 3.76, 2.29, 0.74μg/ml, and corresponding skin concentrations were 1.20, 2.84, 1.92, 0.90 μg/g at 0.5, 1, 2, 4 hours after the drug administration, respectively.

View full abstract

Since quinolones have been reported to have potent convulsant activity, we studied the effect of pazufloxacin (PZFX) on the receptor binding of γ-aminobutyric acid (GABA). PZFX hardly inhibited GABA receptor binding in its high concentration (10^-3M). And non-steroidal anti-inflammatory drugs did not affect the inhibitory activity of PZFX. And the intraventricular injection of PZFX induced convulstion in mice in its high doses, and concurrent administration of 4-biphenylacetic acid (5 nmol) did not affect the convulsant activity of PZFX. These results suggest that PZFX might have very weak convulsant activity.

View full abstract

The effect of pazufloxacin(PZFX), a synthetic new quinolone antimicrobial agent, on blood glucose levels and several factors affected to them was evaluated in rats using single or 28-days repeated administration. The following results were obtained;
1. In preliminary assessment of the evaluation model in rats, the assay system for blood glucoseregulating factors (insulin, etc.) was judged as reliable, since it produced results in an oral glucose loading test consistent with those reported elsewhere. It was found possible to narrow down diurnal variations by introducing fasting from 21: 00 of the previous day. Human test kits used for the measurement of insulin and thyroid hormones were usable for the measurement of these parameters in the blood of rats.
2. In the single administration test, PZFX was found to reach saturation in the blood at a dose of 1200 mg/kg, which corresponded to 100 times the proposed clinical dose. However, no abnormal or specific changes were noted in any biochemical parameters(such as blood glucose, insulin, glucagon and thyroid hormones etc.) or in histopathological examination of the pancreas (islets of Langerhans).
3. In the repeated administration test, a dose of 600 mg/kg(approximately 50 times the proposed clinical dose) repeated once daily for 28 days inhibited body weight gain from the second day until the end of administration. This dose was thus estimated to be high enough to induce toxicity.
4. In the repeated administration test, insulin level tended to increase on the final day of administration. Blood glucose level underwent no change. This seemed to be a phenomenon not associated with the drug. No abnormal or specific changes were detected in other biochemical parameters or in histopathological examination of the pancreas (islets of Langerhans).
The present test results combined with results of earlier toxicity tests suggest that it is unlikely that PZFX exerts the effect on blood glucose levels and blood glucose-regulating factors.

View full abstract

A phase I clinical study on pazufloxacin(PZFX) was conducted in 23 healthy male adults. The single-dose study was started from 20mg in the fasting state, and serially increased to 50, 100, 200 and 400mg. The effect of food intake was investigated by same volunteers in the single-dose study with 200mg. The multiple-dose study was carried out a total of 19 times at a single dose of 300mg given 3 times a day after meals for 7 days. The following results were obtained.
Rash was observed in both the brachia and the inside of a thigh in 1 patient on day 7 in the multiple-dose study. This disappeared within 1 week after withdrawal, showing no abnormal laboratory test values. No other abnormal subjective or objective findings, physical findings, electrocardiographic findings or laboratory test values were observes.
Dose-depentdent changes were observed in the blood levels during the single-dose study in the fasting state with 100, 200 and 400mg of PZFX. The average maximum blood levels were observed between 0.58 and 0.94 hour, 0.944, 2.975 and 4.512 μg/ml, respectively, with half-lives in blood of 2.01-2.48hours. Cmax and AUC were proportionally related with the dose. Urinary excretion rates showed little change with increasing dose, and were 81.2-85.1% at 24 hours after administration. In the study of effects of food intake, Cmax, at 2.97μg/ml in the fasting state, was higher than the postprandial Cmax, 2.02μg/ml, but the postprandial Tmax of 1.20 hours was longer than the fasting value, 0.576 hours. T_1/2in the fasting state was 2.27 hours, longer than the postprandial value(1.88 hours); however, AUC were almost the same in both states. The blood levels reached a plateau on day 1 in the multiple-dose study, 3 times a day for 7 days, and no accumulation was observed on the basis of urinary excretion rates.
Thus, PZFX is considered to have no problem with safety, and, taking into consideration its pharmacokinetics and the microbial activity against various organisms, its clinical evaluation seems warranted.

View full abstract

The effects of a newly developed pyridone carboxylic acid antibacterial agent, pazufloxacin (PZFX), were investigated in six healthy male volunteers. PZFX was given orally in three doses of 300mg each for 7 days.
PZFX did not decrease the level of total bacterial counts in feces. The impact was more marked on aerobic and facultative aerobic components than anaerobic components. PZFX caused a decrease in Megasphaera, Veillonella, Fusobacterium and Clostridium perfringens, but not in Bacteroides fragilis group organisms. Members of the family Enterobacteriaceae decreased markedly during treatment and returned to normal within 1 week after cessation of administration.
Clostridium difficile was recovered sporadically before, during and after administration of PZFX.

View full abstract

We studied the metabolism of pazufloxacin (PZFX) using human plasma and urine of phase I study. The following results were obtained.
1) Trace amount of PZFXM 1, other than unchanged PZFX, was detected in plasma.
2) Unchanged PZFX, PZFXM2, PZFXM3 and PZFX glucuronide were detected in urine.
3) No chiral inversion in body was observed.

View full abstract

Pazufloxacin (PZFX) is a new fluoroquinolone antimicrobial agent. This study was designed to investigate the influence of meal on pharmacokinetics of PZFX and to compare with ofloxacin (OFLX).
The pharmacokinetic studies of PZFX (fasting and after meal) and OFLX (fasting) were performed by a three cross-over design method in six healthy male volunteers. After a 200mg of PZFX or OFLX was orally administered, the serum, salivary and urinary concentrations of each drug were measured.
The result is as follows:
The Cmax of after meal (1.67 μg/ml) on PZFX was lower than that in fasting state (2.96 μg/ml).
The Tmax of after meal (1.61 hour) was longer than that in fasting state (0.85 hour).
The T1/2 of in fasting state (1.91 hour) was almost the same as that of after meal (1.79 hour). The AUC_0-∞of in fasting state (8.65 μg·h/ml) were almost the same as that of after meal (7.15 μg·h/ml). These results suggested that the influence for absorptivity of by meal PZFX was not significant.
The cumulative urinary excretion rates for in fasting state and after meal within 24 hours were 78.8 and 80.7%, respectively. There was no difference between in fasting state and after meal.
This result suggested to be not the influence for absorptivity by meal.
When the serum concentrations of PZFX (fasting) and OFLX (fasting) were compared, the Cmax of PZFX was higher than that of OFLX (2.25 μg/ml). The Tmax of PZFX was almost equal to that of OFLX (0.83 hour). The T1/2of OFLX was 5.35 hour, which was longer than that of PZFX. The AUC_0-∞of OFLX (13.73 μg·h/ml) was higher than that of PZFX.
The cumulative urinary excretion rate for OFLX within 24 hours was 72.0%, which was slightly lower than that for PZFX.
The salivary concentration of PZFX administered in fasting state and after meal were about 1/4 of the serum concentration. The salivary concentration of OFLX was almost the same as the serum concentration. The correlation coefficients of PZFX (fasting), PZFX (after meal) and OFLX (fasting) were respectively with excellent correlation. Since the salivary concentration was well correlated with the serum concentration, and the salivary and serum concentration showed parallel changes, the salivary concentration could be a good merkmal of the serum concentration.

View full abstract

The antibacterial activity and clinical effects of pazufloxacin (PZFX), a new quinolone antimicrobial drug, were investigated. Minimum inhibitory concentrations (MICs) of PZFX were examined against 239 strains of 7 clinically isolated species at 10⁶ cells/ml using plate dilution method. The drug showed 90% minimum inhibitory concentration (MIC90) levels of 0.2 μg/ml, 12.5 μg/ml, 0.1 μg/ml, 3.13 μg/ml, 0.1 μg/ml, 0.1μg/ml, 0.1μg/ml and 0.78 μg/ml against methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant S. aureus (MRSA), Escherichia coli, Serratia marcescens, Kiebsiella pneumoniae, Proteus mirabilis, Morganella morganii and Pseudomonas aeruginosa, respectively. PZFX was administered to 14 patients with respiratory infections diseases at a daily dose of 200-300 mg for 7-21 days, and the clinical effects were investigated. The drug was effective in 12, slightly effective in 1 and ineffective in 1. An efficacy rate was 85.7%. None of the patients had side effects or abnormalities in clinical laboratory tests.

View full abstract

A newly developed fluoroquinolone antimicrobial, pazufloxacin (PZFX), was administered to patients with respiratory tract infection, and its penetration into the serum, sputum and saliva over time, and its clinical effectiveness were evaluated. PZFX was administrated orally to a total of 13 patients, 7 with chronic bronchitis, 3 with bronchiectasis, 2 with secondary infection to bronchial asthma and 1 with acute pneumonia, at a dose of 100 mg or 200mg, 3 times daily, for 7-23 days.
The penetration of PZFX into the sputum and saliva was measured in the 2 patients with bronchiectasis. A dose of 200 mg was administrated 3 times daily for 7 days, and the serum, sputum and salivary concentrations were measured on days 1, 4 and 7.
The range of peak concentrations of PZFX in the serum was 3.19, 4.84 μg/ml respectively and in the sputum was 0.98, 2.20 μg/g respectively, reflecting the clinical response well. The penetration of PZFX from serum to saliva was about 30%. Because this rate is highly correlated with the serum concentrations, its pharmacokinetics can be calculated by saliva.
The clinical efficacy of PZFX was classified good in 12 patients and fair in 1, and the efficacy rate was 92.3%. Bacteriologically, 1 strain each of Serratia marcescens, Haemophilus influenzae, Staphylococcus aureus and Streptococcus pneumoniae, a total of 4 isolates, were eradicated. No side effects or abnormal laboratory findings were observed.

View full abstract

Pazufloxacin (PZFX), a newly synthesized pyridoncarboxylic acid antibacterial agent, was administered to 6 patients with chronic bronchitis, 4 with bronchiectasis, 3 with acute bronchitis, 1 with a secondary infection of diffuse panbronchiolitis and 1 with a secondary infection of pulmonary emphysema, at a single dose of 100 mg or 200 mg twice or three times daily for 6-15 days. The results were excellent in 2, good in 8, fair in 3 and poor in 2, with a total efficacy rate of 66.7%.
Among the causative organisms isolated, i.e., 3 strains of Streptococcus pneumoniae, 3 strains of Moraxella catarrhalis and 1 strain of Pasteurella multocida, 2 strains of S. pneumoniae, 3 strains of M catarrhalis and 1 strain of P. multocida were eradicated, with an eradication rate of 6/7.
Neither side effects nor abnormal laboratory findings were observed in any subjects.
The antimicrobial activity of PZFX against S. pneumoniae, M catarrhalis, Haemophilus influenzae and Pseudomonas aeruginosa, isolated from respiratory tract infections in our department recent years, was compared with that of tosufloxacin (TFLX), ciprofloxacin (CPFX) and ofloxacin (OFLX)[excluding S. pneumoniae in OFLX]. PZFX showed equal or superior antimicrobial activity against M. catarrhalis, H. influenzae and P. aeruginosa, compared with control drugs.

View full abstract

The in vitro antimicrobial activity of pazufloxacin (PZFX), a new-quinolone agent for oral use developed in Japan, and its therapeutic efficacy in the treatment of respiratory tract infections were evaluated. The minimum inhibitory concentrations (MICs) of PZFX, ofloxacin (OFLX), ciprofloxacin (CPFX), tosufloxacin (TFLX), sparfloxacin (SPFX), cefaclor (CCL) and rifampicin (RFP) against 20 strains each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Pseudomonas aeruginosa, 18 strains each of Haemophilus influenzae and Mycobacterium intracellulare, 22 strains each of Mycobacterium tuberculosis and Mycobacterium avium were determined by the micro-broth dilution method using the Dynatech MIC 2000 system. As shown by MICs, PZFX was as active as OFLX against MSSA, MRSA, H. influenzae, E. coli, K. pneumoniae, E. cloacae and S. marcescens. PZFX was more active than OFLX against P. aeruginosa, but less active than OFLX against Mycobacteriaceae. Twenty-eight patients received a daily dose of 300 mg to 600 mg of PZFX per os for 3-14 days (mean: 11.6 days): one patient with acute bronchitis, 10 patients with pneumonia, 11 patients with infection associated with bronchiectasis, 4 patients with infection associated with pulmonary emphysema, and one patient each with infection associated with bronchial asthma et old pulmonary tuberculosis. The clinical effects were excellent in 3, good in 16 and poor in 6 patients (efficacy rate: 76%). Three cases were excluded from clinical evaluation. Twelve strains were identified as causative organisms: Three strains each of S. aureus and H. influenzae, two strains each of Streptococcus pneumoniae and P. aeruginosa, one strain each of Streptococcus Pyogenes and Klebsiella oxytoca. Six of 12 strains were eradicated and one strain was decreased in number by administraion of PZFX. Rash and dizziness were observed in one patient each during treatment with PZFX. Elevation of s-GPT, leucocytopenia, and eosinophilia were observed in one patient each. These adverse reactions disappeared after completion of therapy. We conclude from the above results that PZFX is one of the most useful quinolone agents for oral use as a drug of first choice in the treatment of respiratory infections.

View full abstract

We investigated the effect of an antacid (dried aluminum hydroxide gel, AL) and cimetidine, histamine H2-antagonist on the gastrointestinal absorption of pazufloxacin (PZFX) in 6 healthy male volunteers. 200 mg of PZFX was given orally to fasting subjects with and without 1 g of AL or 200 mg of cimetidine.
The pharmacokinetic parameters for PZFX obtained after each of treatments were as follows: the Cmax, Tmax, T_1/2, AUC_0→∞ and urinary excretion rate for PZFX alone were 4.28μg/ml, 0.88 h, 2.15 h, 8.85 μg ·h/ml and 87.2%, respectively; those for coadministration with AL were 1.77 μg/ml, 1.17 h, 1.98 h, 6.24 μg ·h/ml and 69.7%; and those for coadministration with cimetidine were 2.75 μg/ml, 0.76 h, 2.00h, 8.93 μg ·h/ml and 84.8%.
Gastrointestinal absorption of PZFX was inhibited (58.6% of the Cmax, 29.5% of the AUC_0→∞) by interaction with antacid, but the inhibition was slight compared with that of other quinolone antimicrobial agents. Coadministration of cimetidine resulted in decrease (35.7%) in the Cmax, but the AUC0_0→∞ was not inhibited.

View full abstract

The minimum inhibitory concentration (MIC) of pazufloxacin (PZFX) for Streptococcus pneumoniae was determined. The therapeutic efficacy on respiratory and urinary tract infections were also evaluated. The results were as follows:
1. The MIC of PZFX for S. pneumoniae isolated from blood, sputum, pharyngeal secretion and otorrhea was determined by agar plate dilution method and compared with those of other drugs. The MICH and MIC₉₀ of PZFX against both penicillin-sensitive S. pneumoniae (PSSP) and penicillin-insensitive S. pneumoniae (PISP) were 3.13 μg/ml and 6.25 μg/ml, respectively. The MIC₅₀ and MIC₉₀ of tosufloxacin (TFLX) against PSSP were 0.2 μg/ml and 0.39 μg/ml, respectively, and those against PISP were 0.2 μg/ml and 0.2 μg/ml, respectively. Thus, it was found that the antimicrobial activity of TFLX against both PSSP and PISP was four times stronger than that of PZFX. The MIC of PZFX against strains which were highly resistant to PCG ranged from 3.13 to 6.25 μg/ml. There was no cross resistance between PZFX and PCG in PISP.
2. PZFX was administered to 18 patients with respiratory tract infections and 2 patients with urinary tract infections. The clinical effects could be evaluated in 19 patients except one with pyelonephritis. Excellent or good clinical response was obtained in 2 of 2 patients with pneumonia, 10 of 11 patients with chronic bronchitis, 4 of 4 patients with bronchial asthma with infection, one patient with pulmonary emphysema with infection and one patient with pyelonephritis, with an overall efficacy rate of 94.7%(18/19). Causative bacteria were identified in 3 patients. At the end of the therapy, Erwinia agglomerans persisted in a patient with chronic bronchitis. In another patient with pyelonephritis, all the strains of Pseudomonas aeruginosa, Morganella morganii, Enterococcus faecalis, Proteus mirabilis and Klebsiella pneumoniae were eradicated. Bacteriological effect remained unknown in a patient with pseudomonas urinary tract infection who was excluded from clinical evaluation. With regard to side effect, an eruption accompanied with eosinophilia was observed in a patient on the fourth day of the treatment, and the drug was withdrawn.

View full abstract

Laboratory and clinical studies were performed on a new quinolone derivate, pazufloxacin (PZFX).
The in vitro antivacterial activity of PZFX was evaluated against clinically isolated strains, and compared with those of norfloxacin (NFLX), ofloxacin (OFLX) and ciprofloxacin (CPFX). Against methicillin-resistant Staphylococcus aureus (MRSA; 8 strains) and Escherichia coli (9 strains), PZFX was almost equal to reference compounds. Against Klebsiella pneumoniae (13 strains), PZFX was superior to reference compounds. Against Pseudomonas aeruginosa (17 strains), PZFX was inferior to CPFX and superior to NFLX and OFLX.
PZFX was administered to 4 patients (2 with acute tonsillitis, 1 with acute pharyngolaryngitis and 1 with pneumonia) orally at the dose of 100mg two or three times a day for five days. The clinical efficacy was good in all 4 cases. The causative organism was eradicated in 2 cases and unevaluable in 2.
As for adverse reactions, a slight epigastric discomfort was observed in 1 case. No abnormal laboratory findings were found in any cases.

View full abstract

Laboratory and clinical studies of pazufloxacin (PZFX), a newly developed synthetic antibacterial agent of quinolone derivative, were performed.
MICs of this and 8 other control drugs against 340 strains of 14 species of bacteria were determined. Among gram-positive bacteria, MIC₉₀ of this drug against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Staphylococcus epidermidis were 0.20, 12.5, 0.39 μg/ml respectively, and the antibacterial effect ranked next to that of tosufloxacin (TFLX). The antibacterial effect on other gram-positive bacteria was, however, slightly weaker than those of control drugs.
Against gram-negative bacteria, on the other hand, the antibacterial effect on Haemophilus influenzae and Escherichia coil, were excellent with MICs of ≤0.025 μg/ml. The antibacterial effect on other gramnegative bacteria was almost equal to that of TFLX. Against Pseudomonas aeruginosa which showed MICs more than 6.25 and 25 μg/ml respectively with imipenem and gentamicin, the antibacterial effect was superior to those of other control drugs with MIC₉₀ of 3.13 μg/ml.
In the clinical study, 11 cases of respiratory infection and 2 cases of urinary infection were studied. The clinical effect was excellent in 3 cases and good in 10 cases with the effective rate of 100%. All bacteria detected in 3 cases were eradicated. As for side effects, headache and nausea were noted in 1 case. In addition, increased GOT, GPT, ALP, γ-GTP, and LAP were observed in 1 case.

View full abstract

The antimicrobial activity, absorption, excretion and clinical effect of pazufloxacin (PZFX), a newly developed quinolone derivative were studied, and the following results were obtained.
1) Antimicrobial activity
The antimicrobial activity of PZFX against 150 strains of clinically isolate was determined. The MIC90 of PZFX was 0.78μg/ml for methicillin-susceptible Staphylococcus aureus (MSSA), 3.13μg/ml for methicillin-resistant S. aureus (MRSA), 0.1μg/ml for Escherichia coli, 0.78μg/ml for Klebsiella pneumoniae, 0.2μg/ml for Proteus mirabilis and 6.25μg/ml for Pseudomonas aeruginosa.
2) Absorption and excretion
PZFX was administered to 3 healthy male adults at a single dose of 200 mg once, or 3 times a day after meals for 7 days, and the levels in saliva, sweat and urine were determined. The maximum blood level in the single dose study was 2.0-2.5μg/ml at 0.5-7 hours after administration, and 2.1-2.7μg/ml at 2-3 hours in the multiple dose study, showing no significant difference. Although transfer of this drug to saliva was almost as good as that to blood, the rate of transfer to sweat was slightly slower than that to blood.
The urinary recovery rate of PZFX in the single dose study was as high as 76.6-87.7% at 8 hours after administration, and no accumulation was observed in the multiple dose study.
The Cmax of PZFX in blood tended to be slightly lower when ingested with green tea or milk, however, it did not affect AUC or urinary excretion rate.
3) Clinical results
The clinical effect was evaluated in 11 patients including 5 with bacterial pneumonia, 3 with chronic bronchitis, 1 with acute pharyngitis, 1 with secondary infection of old pulmonary tuberculosis and 1 with infectious mononucleosis. PZFX was effective in 9 and unevaluable in 1, an efficacy rate of 90%. Bacteriologically, strains of S. aureus isolated from 2 patients with bacterial pneumonia and Streptococcus Pyogenes from 1 with acute pharyngitis were all eradicated. No objective or subjective side effects were observed except for 1 case each of mild elevation of GOT and platelet count on laboratory testing.
Thus, this drug was demonstrated to possess a wide antimicrobial spectrum and favorable pharmacokinetics, and proved to be a useful drug for infections in internal medicine.

View full abstract

We studied a newly developed oral quinolone antimicrobial agent, pazufloxacin (PZFX), and obtained the following results
1) Serum and urinary levels of PZFX were determined after oral administration of PZFX 200 mg to 4 aged patients with renal dysfunction. The decrease of serum concentrations of PZFX were correlated with the severity of renal dysfunction (Ccr: 81.6, 63.9, 16.8 and 7.0ml/min). T_1/2 was prolonged (4.21, 8.13, 7.05 and 10.81 hours), and AUC_0-∞was increased (12.42, 33.51, 61.42 and 53.03μg/ml) with the severity of renal dysfunction. The urinary recovery rates of PZFX were 65.1, 73.2, 71, and 12.1% within the first 24 hrs, with the lowest rate seen in a patient with severe renal dysfunction. PZFX was administered to 36 patients with respiratory tract infection and 1 with urinary tract infection. Clinical response was good in 34 and poor in 3, and the efficacy rate of 91.9%. Laboratory tests revealed elevation of GPT in 1, eosinophilia in 1 and a rise of reticulocyte. However, these findings were slight, and no adverse reaction caused by the drug was observed.

View full abstract

We performed bacteriological and clinical studies on pazufloxacin (PZFX), a new quinolone derivative, in respiratory tract infections and obtained the following results.
1) The MIC₉₀ of PZFX against Staphylococcus aureus, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae and Pseudomonas aeruginosa were 0.03-4μg/ml, which were almost equal to those of sparfloxacin (SPFX) and levofloxacin (LVFX). The MIC against methicilline resistant S. aureus and Streptococcus pneumoniae were inferior to those of SPFX and LVFX.
2) Ten patients with respiratory tract infections were treated with PZFX. The effect of the agents on the infections was good in nine, unevaluable in one.
No adverse reaction was obtained in any of the patients.
Abnormal laboratory findings were observed in 2 patients with mild liver damage.

View full abstract

We studies the effect of pazufloxacin (PZFX), a new oral pyridone-carboxylic acid derivative, on the serum concentration of theophylline (TP) in 5 healthy male volunteers.
In advance, TP alone was given orally for four days at a daily dose of 400mg b. i. d., then the serum samples were obtained as a control. From the 5th day of TP administration, concomitant administration of PZFX at a daily dose of 200mg t.i.d. was started. Blood was drawn on the 3rd and 5th days of the concomitant administration, and the serum concentrations of TP were compared with that of control.
On the 3rd and 5th days of the concomitant administration, no significant difference were observed in any pharmacokinetic parameters such as AUC, Cmax and C1TB of TP. No objective nor subjective side effect was observed throughout the experimental period.
According to above results, we concluded that PZFX is safe drug when it is administered concomitantly with TP.

View full abstract

We performed laboratory and clinical studies on pazufloxacin (PZFX), a new oral quinolonecarboxylic acid, with the following results.
1) Minimal inhibitory concentrations (MICs) of PZFX were measured for 238 clinical isolates, and compared with those of sparfloxacin (SPFX), levofloxacin (LVFX), tosufloxacin (TFLX) and ciprofloxacin (CPFX). Against methicillin-sensitive Staphylococcus aureus, the antimicrobial activity of PZFX was superior to that of CPFX. Many strains of methicillin-resistant S. aureus and Enterococcus faecalis were resistant to PZFX and other reference agents. The MICs of PZFX as well as other agents were relatively high for Pseudomonas aeruginosa. However, PZFX exhibited high activity against gram-negative bacteria with low MICs which were similar to those of CPFX.
2) The clinical efficacy of PZFX was evaluated for a total of 17 patients. Five with pneumonia, 3 with acute bronchitis, 2 with chronic bronchitis, 1 with acute tonsillitis, 2 with acute pharyngolaryngitis, 2 with acute cystitis, 1 with acute pyelonephritis and 1 with infected atheroma were treated with PZFX. The patients consisted of 9 males and 8 females aged 24 to 82 years, and most of them had underlying diseases. The patients were given a dose of 100 to 200 mg, b.i.d. or t.i.d. for 2 to 21 days. The clinical response was excellent in 3 cases, good in 8, fair in 4, poor in 1 and unknown in 1. The clinical efficacy rate was 69%. Bacteriologically, 7 strains isolated from infections were eradicated by treatment with PZFX. The side effects observed in 5 cases were nausea/vomiting, abdominal discomfort in 2 cases, anorexia/epigastralgia and general fatigue, respectively. Slight elevation of GOT, GPT and an increase in eosinophil count were observed in 2 cases.

View full abstract

A clinical study of a new oral quinolone synthetic antimicrobial drug, pazufloxacin (PZFX), was conducted in 8 patients with respiratory infectious diseases, and a basic study was performed to examine the change in its serum level in 11 patients.
1. Clinical study PZFX was administered to 8 patients with respiratory infectious diseases (5 with pneumonia, 3 with chronic respiratory tract infection) at 600 mg a day (3 divided doses) for 7-15 days, to a total dosage of 4.2-8.6g.
Clinical effects were excellent in 3, good in 4 and fair in 1. Pseudomonas aeruginosa and Serratia marcescens were isolated from 1 patient and both were eradicated. No side effects or abnormal laboratory findings were observed in the patients.
2. Pharmacokinetic study
The time-course change of PZFX (200 mg) in serum was determined in a single-dose study by HPLC in a patient of 49 years old and 10 aged patients with chronic respiratory diseases (5 with pulmonary tuberculosis, 2 with bronchial asthma, 1 each with chronic bronchitis, bronchiectasis, pulmonary emphysema and atypical mycobacteriosis), and the pharmacokinetics were studied. The average serum level after administration in a patient of 49 years old was 2.00μg/ml at 1 hour, 2.59μg/ml at 2 hours, 1.19μg/ml at 4 hours and 0.46μg/ml at 6 hours and in the 10 patients the mean average was 0.966±0.657μg/ml at 1 hour, 2.263±1.064μg/ml at 2 hours, 2.782±1.041μg/ml at 4 hours and 1.489±0.534μ/ml at 6 hours, and the peak level was observed at 3.2 hours. Cmax was 3.122±1.002μg/ml, T_1/2 2.740±0.841 hr and AUC_0-∞16.75±4.32μg·hr/ml. These results show that the serum concentration of PZFX exceeds MICs of many causative organisms in respiratory infections, suggesting its clinical usefulness, and were almost consistent with the data of healthy adults obtained in the phase I clinical study, excluding AUC, Tmax; i.e., of 2 patients who showed mild renal dysfunction, 1 demonstrated elevation of AUC, and the other showed prolongation of T_1/2 and elevation of AUC.

View full abstract

Basic and clinical studies were performed on a new quinolone antimicrobial agent for oral use, pazufloxacin (PZFX). The results were as follows.
1. Antimicrobial activity: The minimal inhibitory concentrations of PZFX against 515 clinical isolates including 16 different species were measured and compared with those of ofloxacin, norfloxacin and ciprofloxacin. PZFX showed good antimicrobial activity against gram-positive and-negative bacteria.
2. Blood and sputum concentrations: A single dose of 200 mg and 100 mg of PZFX was orally administered after a meal to 4 patients and 1 patient, respectively. The blood and sputum concentrations of PZFX were measured by high pressure liquid chromatography. In 4 patients given 200 mg, the peak concentrations in blood and sputum were 1.80-3.20μg/ml at 2-4 hours after administration and 0.57-1.09μg/g at 2-5 hours, respectively, suggesting that PZFX had good penetration into sputum.
3. Clinical efficacy: PZFX was administered to 14 patients with respiratory infections and 1 patient with urinary tract infections, and its clinical efficacy and side effects were investigated. The efficacy rate was 85.7% in the respiratory infection group (excellent in 2, good in 10, and poor in 2). Abnormal findings in clinical testing were mild elevation in GOT and GPT, and in BUN and s-Cr in 1 patient each. These abnormal changes improved after completion of treatment, and the safety of PZFX was confirmed. No side effects were observed.

View full abstract

We evaluated the usefulness of pazufloxacin (PZFX), a new quinolone derivative, in respiratory tract infections. The MIC₅₀ of PZFX for methicillin-sensitive Staphylococcus aureus was 0.39μg/ml. It was 12.5μg/ml for methicillin-resistant S. aureus, 3.13μg/ml for Streptococcus pneumoniae, 0.013μg/ml for Haemophilus influenzae, 0.025μg/ml for Moraxella catarrhalis and 1.56μg/ml for Pseudomonas aeruginosa.
The activity was comparable with or superior to that of ofloxacin (OFLX).
The pharmacokinetics of PZFX were studied in two patients. The maximum sputum levels during a 200mg oral administration three times per day were 0.72μg/g and 2.27μg/g.
Twelve patients with lower respiratory tract infections were studied for clinical evaluation of PZFX. PZFX was given orally at 300-600 mg per day for 3-7 days. The causative organisms were S. pneumoniae (2 cases), H. influenzae (3 cases), M. catarrhalis (1 case) and P. aeruginosa (2 cases). The rate of clinical response was 81.8%. Two strains of S. pneumoniae and 2 strains of P. aeruginosa were not eliminated in sputum samples. Diarrhea was observed in one case.
We concluded that PZFX is a useful oral antimicrobial agent for the treatment of respiratory tract infections.

View full abstract

We investigated pazufloxacin (PZFX), a newly developed oral quinolone, for its antimicrobial activity, for its pharmacokinetics in the plasma and sputum, and for its clinical efficacy on respiratory infections. The results were as follows.
1. Antimicrobial activity: Minimal inhibitory concentrations of PZFX against 740 strains of 18 species isolated from clinical specimens (170 strains of gram-positive cocci, 319 of enterobacteria, 125 of glucose non-fermenting gram-negative rods, 49 of Moraxella catarrhalis, 52 of Haemophilus influenzae, 25 of Bacteroides fragilis) were determined according to the standard method prescribed by the Japan Society of Chemotherapy, and compared with those of tosufloxacin (TFLX), ofloxacin (OFLX) and lomefloxacin (LFLX). The overall antimicrobial activity of PZFX was superior to OFLX and LFLX, and almost equal to or slightly less than TFLX.
2. Blood and sputum levels
When 200 mg of PZFX was orally administered to a patient with bronchiectasis (48 years old, male, 50kg) after meals, the maximum blood concentration was 3.38μg/ml at 4 hours, and the maximum level in sputum was 1.35μg/g. The rate in sputum against the maximum blood concentration of PZFX was 39.9%.
3. Clinical results
PZFX was administered to 4 patients with respiratory infections at a dose of 200-600 mg a day for 7-14 days. The clinical efficacy was good in all patients. No side effects or abnormal laboratory findings were observed.

View full abstract

We performed a basic evaluation of pazufloxacin (PZFX), a newly developed new quinolone agent, and clinically studied its application in the treatment of respiratory infections, with the following results.
1. Antibacterial activity
The minimum inhibitory concentrations (MICs) of PZFX against 272 strains of 12 species isolated from clinical material were measured and compared with those of other new quinolone agents, ofloxacin (OFLX), tosufloxacin (TFLX) and ciprofloxacin (CPFX). The antimicrobial activity of PZFX for grampositive coccus was the same as that of OFLX and for gram-negative rod was slightly better than those of TFLX and CPFX.
2. Clinical efficacy
Ten patients with respiratory tract infections were given PZFX for 4 to 15 days. Clinical efficacy was assessed as good in 9 cases and poor in 1 case. No side effects were observed.

View full abstract

Microbiological and clinical studies of a new quinolone antimicrobial for oral use, pazufloxacin (PZFX), were performed.
1) Microbiological study; The minimum inhibitory concentrations (MICs) of PZFX were determined against 5 species of gram-positive cocci and 7 species of gram-negative rods which had been isolated from urinary tract infections and stored in our department. The MICs of PZFX were compared with those of ofloxacin (OFLX), tosufloxacin (TFLX) and ciprofloxacin (CPFX). The antimicrobial activity of PZFX was about the same as that of OFLX against gram-positive cocci and Pseudomonas aeruginosa, which was superior to that of OFLX against gram-negative rods except P. aeruginosa.
2) Clinical study; PZFX was administrated to the following patients, and its clinical efficacy and side effects were investigated: 1 patient with acute uncomplicated pyelonephritis at a dose of 100 mg 3 times a day for 14 days, 1 with acute uncomplicated cystitis (a female) at a dose of 200 mg 3 times a day for 4 days, and 16 with complicated urinary tract infections at a dose of 100-200 mg, 2-3 times a day for 4-7 days. The efficacy was excellent in acute uncomplicated pyelonephritis and acute uncomplicated cystitis. Efficacy, as evaluated by the criteria of the Japanese UTI Committee in 14 of 16 patients with complicated urinary tract infections, was excellent in 9 and good in 2 patients. The overall effectiveness rate was 78.6%, showing the rating of ‘excellent’ in 64.3%. 18 of 21 strains of urinary isolates were eradicated, an eradication rate of 85.7%.
Leucocyte counts were decreased in 1 of a total of 18 patients. No subjective or objective side effects were observed.

View full abstract

We investigated the influence of urine components, such as pH, magnesium concentration and calcium concentration, on the antimicrobial activity of pazufloxacin (PZFX), and the influence of PZFX on the bactericidal activity of leukocytes. We also studied the clinical efficacy of PZFX for urinary tract and genital infections in order to clarify its usefulness in such infections.
1. Influence of urine pH and cations on antimicrobial activity of PZFX We investigated the antimicrobial activity of PZFX in human urine and the influence of urine components (pH, magnesium concentration and calcium concentration) on the antimicrobial activity of PZFX. Two bacterial strains, Escherichia coli NIHJ JC-2 and Pseudomonas aeruginosa 18S, were tested. The MBC of PZFX in urine was higher than in Miieller-Hinton broth against these two strains. However, no influence of urine components on the MBC of PZFX was seen in E. coli. On the other hand, the MBC of PZFX against P. aeruginosa was low when urine pH was high.
2. Influence of PZFX on bactericidal activity of leukocytes Polymorphonuclear leukocytes (PMNs) and monocytes isolated from a healthy volunteer were stimulated by phorbol myristate acetate (PMA) or opsonised zymosan in the presence or absence of PZFX, and the superoxide anion generation of PMNs and monocytes was measured by the chemiluminescence method.
The bactericidal activity of PMNs was enhanced by PZFX.
3. Clinical study of PZFX in urinary tract and genital infections PZFX was administered to eighteen patients with urinary tract and genital infections. The clinical efficacy of PZFX was evaluated by determining symptoms, pyuria, bacteriuria and blood test results before and after the administration of PZFX. One patient with acute uncomplicated cystitis and two patients with acute prostatitis showed excellent response, and one patient with acute uncomplicated pyelonephritis showed moderate response. Thirteen patients with chronic complicated urinary tract infections were evaluated according to the criteria of the UTI Committee, and the overall efficacy rate was 84.6%(excellent: 30.8%, moderate: 53.8%, poor: 15.4%). 23 strains of 9 species were isolated from the patients with chronic complicated urinary tract infections, and 19 strains were eliminated. As to side effects, one case of slight dizziness was observed. No abnormal laboratory findings were caused by PZFX.
These results indicated that PZFX enhances the in vivo bactericidal effect of leukocytes and is a useful antimicrobial agent for urinary tract and genital infections. We should examine the clinical effect of PZFX on urinary tract infections, paying attention to the urine pH of the patients.

View full abstract

Pazufloxacin (PZFX) was administered to 36 patients with chronic complicated urinary tract infections, acute uncomplicated cystitis and acute prostatitis to investigate its therapeutic effect and safety. Efficacy was judged according to the criteria of Japanese UTI Committee. Clinical efficacy in complicated UTI was excellent in 16, moderate in 10 and poor in 2 patients with the overall efficacy rate of 92.9%. In acute uncomplicated cystitis, it was excellent. According to the attendant docter's evaluation, clinical efficacy in a acute prostatitis was good. Neither side effects nor abnormal laboratory fingings was not observed.

View full abstract

Pazufloxacin (PZFX), a new family of oral newer quinolones, was tested for the in vitro activity on several strains of Pseudomonas aeruginosa isolated from UTI. For clinical evaluation, the drug was administered in the treatment of UTI, prostatitis. The results obtained were shown in the following
1) In vitro activity on several clinical isolates of P. aeruginosa: The MIC values on the strains tested, varied according to the pH values of medium. When comparing with other conventional drugs, the in vitroactivity of PZFX was less influenced by the culture medium than the other control drugs. The MIC values of PZFX had a tendency to more active in acid media than in alkaline media.
2) Penetration into human prostatic fluid after intake of 200 mg of PZFX: Average concentration (μg/ml) of prostatic fluid (PF) was 0.18 ± 0.11 (n=4) at 1 hour, and it was 0.20 (n=2) at 2 hours. The ratio between PF/serum was 0.12± 0.11 (1h), 0.26 (2 h) respectively.
3) Patients with genitourinary tract infection were treated with oral administration of PZFX 50-200 mg b.i.d. or t.i.d. after meal for 3-14 days. According to the criteria proposed by the Japanese UTI Committee, the overall clinical efficacy of PZFX was 100%(14/14) in uncomplicated UTI, 90%(18/20) in complicated urinary tract infection and 3/3 in prostatitis.
4) For safety, mild loose stool was observed in one patient, during the course of therapy. Laboratory abnormal values were detected for slight elevation of GPT in one case, also that of GOT, GPT and AlP in the other case.

View full abstract

We evaluated the clinical efficacy of pazufloxacin (PZFX) in the treatment of urinary tract infections and measured its in vitro antibacterial activity.
1. The antibacterial activity of PZFX against clinical isolates from patients with urinary tract infections was compared with that of control drugs: norfloxacin (NFLX), ofloxacin (OFLX) and ciprofloxacin (CPFX). The antibacterial activity of PZFX against Staphylococci was superior to those of NFLX, OFLX and CPFX, and against Enterococcus faecalis was inferior to that of CPFX and similar to those of NFLX and OFLX.
2. Two patients with uncomplicated cystitis were treated with PZFX 50-100 mg t.i.d. for 3 days, and twelve patients with complicated urinary tract infections were treated with 100 mg t.i.d. for 4 to 6 days. According to the criteria proposed by the Japanese UTI Committee, the overall clinical efficacy of PZFX was 100% in uncomplicated cystitis and 92% in complicated urinary tract infection. No side effects were observed. Elevation of GOT was noted in one patient, and a decrease in K was noted in one patient.
We concluded that PZFX was a safe, effective drug for urinary tract infections.

View full abstract

We studied the concentration of pazufloxacin (PZFX), a new oral quinolone, in the prostate and its clinical efficacy in the field of urology. The results were as follows.
1. PZFX was administered to 6 healthy male volunteers at a dose of 200 mg. The concentration in the prostatic fluid was 0.32 ± 0.16 μg/ml (mean ± SD) 1 hour after oral administration, and the ratio of prostatic fluid concentration to serum level was 0.11 ± 0.06.
2. The concentration of PZFX in the prostatic tissue was studied in 21 patients with benign prostatic hypertrophy.
The maximum concentration was 2.38± 1.49 μg/g 1 hour after oral administration of the drug at a dose of 200 mg, and the ratio of prostatic tissue concentration to serum level was 0.90±0.14.
3. PZFX was administered to 10 patients with complicated UTI, 6 with acute uncomplicated UTI, 3 with epididymitis and 1 with acute prostatitis. According to the criteria proposed by the Japanese UTI Committee, the clinical efficacy in 6 complicated UTI cases was excellent in 5 and poor in 1, and in 3 acute uncomplicated cystitis cases it was excellent in 2 and moderate in 1. In one acute prostatitis and 2 of 3 with acute epididymitis it was good.
4. No side effect was observed, but elevation of serum GPT and γ-GTP was observed in 1 case.

View full abstract

We studied the antibacterial activity and efficacy of pazufloxacin (PZFX), a new quinolone, in the urological field.
1) Antibacterial activity: The MICs of PZFX were measured against 207 clinical isolates of 14 species from urinary tract infections and compared with those of norfloxacin (NFLX) and ofloxacin (OFLX). In general, the antibacterial activity of PZFX was superior or equal to those of NFLX and OFLX.
2) Statistical studies were performed on Pseudomonas aeruginosa isolated from patients with urinary tract infection from 1983 to 1991. Antibacterial activities of PZFX, NFLX and OFLX against these strains were annually reduced both in Muller-Hinton broth (MHB) and in artificial urine (AU). Antibacterial activities of these new quinolones in AU were more reduced than those in MHB, but the antibacterial activity of PZFX was less reduced in AU than those of NFLX and OFLX in AU. It was considered that the antimicrobial activities of the new quinolones were reduced due to low pH and high concentrations of magnesium and calcium in AU.
3) Clinical efficacy: According to the criteria of the Japanese UTI Committee, the overall clinical efficacy rate was 71% (12/17) for chronic complicated UTI. Bacteriologically, 19 of 23 strains (83%) isolated were eradicated.
4) Side effects: No clinical adverse reactions and no abnormal laboratory findings were noted.

View full abstract

We investigated the antimicrobial activity and clinical efficacy of pazufloxacin (PZFX), a new fluoroquinolone, in urinary tract infections. The antimicrobial activity of PZFX against 270 clinically isolated of 9 species from patients with urinary tract infections (UTIs) was compared with that of norfloxacin, ofloxacin, tosufloxacin and ciprofloxacin. PZFX showed potent antimicrobial activity against gramnegative bacteria. In the most cases, the MICs of PZFX were lower or equal to those of the reference drugs. Five patients with complicated urinary tract infections were treated with PZFX, and clinical efficacy was evaluated according to the criteria proposed by the Japanese UTI Committee. The overall efficacy rate was 80%. Bacteriologically, 4 of 5 strains were eradicated in 5 patients with complicated UTI. The only adverse reaction observed mild rash in one case. Slight abnormal laboratory findings were observed in one case.
We concluded that PZFX was an effective and safe drug for the treatment of urinary tract infections.

View full abstract

We evaluated the in vitro antimicrobial activity, pharmacokinetics and clinical efficacy of pazufloxacin (PZFX), a new oral fluoroquinolone, and the following results were obtained.
1) In vitro antimicrobial activity of PZFX
The antimicrobial activity of PZFX against 330 strains isolated from patients with urinary tract infection (UTI) was measured by the agar dilution method at an inoculum size of 10⁶cfu/ml and compared with those of ofloxacin (OFLX) and tosufloxacin (TFLX). MICs (μg/ml) for 90% of tested strains (MIC90) of PZFX against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci (CNS), Enterococcus faecalis, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were 12.5, 12.5, 25, ≤0.10, 1.56, ≤0.10, 1.56, 25, 1.56, ≤0.10 and 50, respectively. PZFX was the most active against MRSA, CNS, C. freundii, K. pneumoniae, E. cloacae, S. marcescens, P. vulgaris and P. aeruginosa. Against E. faecalis PZFX was fourfold more active than TFLX, and against E. coli PZFX was twice as active as OFLX. The antimicrobial activity of PZFX against P. mirabilis was comparable to that of OFLX, but inferior to that of TFLX.
2) Pharmacokinetics of PZFX
Serum levels and penetration of PZFX into human cerebrospinal fluid (CSF) were examined in 5 cases. Serum and CSF were collected 3 hours after oral administration of PZFX at a dose of 300mg. The concentration of PZFX was measured by HPLC. The mean CSF level was 0.11μg/ml, and mean ratio of CSF level to serum level was 0.04. These results displayed penetration of PZFX into CSF was relatively small.
3) Clinical efficacy of PZFX in UTIs
3. patients with uncomplicated cystitis, 15 patients with complicated UTI and 1 patient with prostatitis were treated with this drug. The efficacy of PZFX evaluated by chief doctor was as follows; excellent in 1 and good in 2 patients with uncomplicated cystitis; excellent in 8, good in 2, fair in 1, poor in 3 patients with complicated UTI and good in 1 patient with prostatitis. The efficacy rate in 14 cases of complicated UTI according to the criteria proposed by the Japanese UTI Committee was 71.4%.
4) Adverse reactions and laboratory findings
No adverse reaction was observed in any case. In laboratory findings, eosinophilia, increased urinary protein and elevated urinary NAG level were noted in one case each.

View full abstract

We performed laboratory and clinical studies on pazufloxacin (PZFX). The antibacterial activities of PZFX against clinical isolates were tested and compared with those of cefaclor (CCL), ofloxacin (OFLX) and tosufloxacin (TFLX).
The MICs of PZFX against coagulase-positive staphylococci ranged from 0.1 to 50μg/ml. The MICs of PZFX against coagulase-negative staphylococci ranged from 0.8 to 25μg/ml. These activities against coagulase-positive and-negative staphylococci were twofold inferior to those of TFLX and comparable or twofold superior to those of OFLX. Most strains of MRSA were not susceptible to PZFX. The antibacterial activities of PZFX against Escherichia coli were very good with the MIC range of ≤0.05 to 6.25μg/ml. The MICs of PZFX against Klebsiella pneumoniae were also very low values and ranged from ≤0.05 to 0.2μg/ml. The MICs of PZFX against Enterobacter cloacae ranged from ≤0.05 to 100μg/ml. The MICs of PZFX against resistant strains (nine of twenty seven strains) ranged from 6.25 to 100μg/ml, but against other strains the MICs of PZFX ranged from ≤0.05 to 0.2μg/ml.
The MICs of PZFX against Pseudomonas aeruginosa ranged from ≤0.05 to 50μg/ml, but against most strains (twenty two of twenty seven) they ranged from 0.4 to 1.56μg/mi. These activities against P.aeruginosa were comparable to those of TFLX and twofold superior to those of OFLX.
The serum concentrations of PZFX in these clinical cases were measured. In the cases of 100mg administration, serum concentrations ranged from 0.239 to 1.48μg/ml. In those of 200 mg administration, serum concentrations ranged from 0.72 to 4.17μg/ml.
In one case, nausea appeared when PZFX was administered, but no additional treatment was needed and administration was continued. No other side effects were noted.

View full abstract

Basic (transfer into gallbladder tissue) and clinical studies of pazufloxacin (PZFX), a newly developed piribone-carboxylic acid antimicrobialagent for oral use, were performed.
The subjects were 6 patients with cholecystolithiasis with normal liver function who were scheduled for cholecystectomy. PZFX was orally administered in the fasting state preoperatively at a dose of 200mg, and 2 hours later, its serum and gallbladder tissue concentrations were measured. Evaluation was possible in 4 patients. The mean serum concentration was 0.20±0.25μg/ml (0.04-0.57μg/ml), and the mean tissue concentration was 0.26±0.22μg/ml (0.11-0.57mg/g). The mean ratio of the tissue concentration to the serum concentration was 2.22±1.27 (1.00-3.75)
The efficacy of PZFX in 14 patients with surgical infection was excellent in 2 patients, good in 9, fair in2 and unevaluable in 1. The efficacy rate was 84.6%(11/13).
Bacteriologically, six strains (2 strains of Staphylococcus aureus, one strain of Escherichia coli, 2 strains of Peptostreptococcus, and one strain of Bacteroides fragilis) were isolated from five patients, and all strains were eradicated after the treatment.
No side effects were observed during medication. The only abnormal finding on clinical tests was an lymphocytosis in one patient.
These findings indicate that PZFX is effective in treating surgical infection. As for transfer of PZFX into gallbladder tissue, further study will be needed.

View full abstract