The in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), anew injectable quinolone, were compared with those of ofloxacin (OFLX), ciprofloxacin (CPFX), imipenem (IPM), ceftazidime (CAZ), gentamicin (GM), and minocycline (MINO).
In gram-positive bacteria, the MIC₉₀s of PZFX mesilate against Staphylococcus aureus and Staphylococcus epidermidis ranged from 0.25 to 4 μg/ml. The antibacterial activity of PZFX mesilate against methicillin-resistant S. aureus (MRSA) was the most potent (MIC₉₀: 16 μg/ml) among the agentstested.
The antibacterial activity of PZFX mesilate against gram-negative bacteria including Enterobacteriaceae and IPM-and GM-resistant Pseudomonas aeruginosa was comparable to that of CPFX, and superior to that of the other agents.
When the MIC of PZFX mesilate for the parent strain was compared with the MIC of quinoloneresistant P. aeruginosa (nfxA, nfxB, nfxC and nalB), the increase in MIC for the nfxB mutant was lower than for the other mutants.
Uptake of PZFX mesilate by S. aureus was unaffected by the addition of carbonyl cyanide-m-chlorophenyl hydrazone (CCCP), in contrast to CPFX.
PZFX mesilate showed potent bactericidal activity in a short period, and it also showed a longer postantibiotic effect (PAE) at high drug concentrations and in short periods than the other agents.
PZFX mesilate showed a potent protective effect against systemic infection in mice caused by gram-positive and-negative bacteria, including MRSA, and IPM-, GM-resistant P. aeruginosa, which reflected its in vitro antibacterial activity. PZFX mesilate also showed a potent therapeutic effect against pulmonary and urinary infection in mice, that exceeded expectations based on the MIC.

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The in vitro activity of pazuoxacin (PZFX) as the active form of pazuoxacin mesilate, a new compound for intravenous administration, was compared with that of tosuoxacin (TX), ciprooxacin CPFX), ceftazidime (CAZ), and imipenem (IPM) against anaerobic clinical strains isolated from 1994 to 1997.
Generally, PZFX was less active than IPM and TX, and equally active as CPFX and CAZ. In some species, PZFX was more active than CAZ.
PZFX displayed good antimicrobial activity against strains of Clostridium perfringens, Fusohacterium nucleatum, some species of Peptostreptococcus, Porphyromonas spp., some species of Prevotella, and Propionibacterium acnes. PZFX inhibited 90 % of the strains of those species at concentrations up to 1.56μg/ml. PZFX was less active against the Bacteroides fragilis group and Prevotella hivia, inhibiting 50 % of the strains of those species at the concentrations up to 6.25 μg/ml. No significant differences in susceptibility were observed between strains of the Bacteroides fragilis group isolated before 1991 and after 1994.

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Pazufloxacin is an injectable new quinolone with a broad spectrum of antibacterial activity.
The MICs of pazufloxacin for 50% of the clinical isolates tested were 3.13μg/ml for Streptococcus agalactiae, 6.25μg/ml for Gardnerella vaginalis, 0.025μg/ml for Escherichiu coli, 0.78μg/ml for Pseudomonas aeruginosa, 6.25μg/ml for Peptostreptococcus magnus, 6.25μg ml for Bucteroides fragilis and 12.5 μg/ml for Prevotella bivia. The MICs of pazufloxacin for 90 % of the clinical isolates tested were 3.13 μg/ml for S. agalactiae, 6.25 μg/ml for G. vaginalis, 0.10 μg/ml for E. coli, 12.5 μg/ml for P. aeruginosa, 25 μg/ml for P. magnus, 12.5 fig/ml for B. fragilis and 25 μg/ml for P. hivia. The results of this study suggest that, subject to confirmation by clinical trials, pazufloxacin, in combination with an agent with reliable activity against anaerobic bacteria, issuitable as empirical therapy of patients with obstetric and gynecological infections.

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The in vitro and in vivo antibacterial activity of pazufloxacin mesilate (PZFX mesilate), a new parenteral fluoroquinolone, was evaluated and compared with that of levofloxacin (LVFX), ciprofloxacin (CPFX), imipenem (IPM), and other parenteral antibiotics.
PZFX showed a broad antibacterial spectrum against gram-positive and-egativeorganisms.
The in vitro antibacterial activity of PZFX was almost equal to that of CPFX and LVFX anddid not show cross-resistance to the parenteral β-lactam antibiotics, IPM, flomoxef (FMOX), and ceftazidime (CAZ). The therapeutic effect of PZFX mesilate against systemic infections in mice was evaluated and compared with that of reference agents. Against infection with gram-negative bacteria, PZFX mesilate and CPFX were the most effective among the agents tested, with 4 to 120 times superior ED₅₀, values to IPM. Against infections with 3 strains of Staphylococcus aureus, PZFX mesilate was almost as effective as FMOX and more effective than LVFX and CPFX. The optimal dose regimen of PZFX mesilate for infections in mice was investigated. The 50 % effective dose obtained by single SC administration was 2 to 4 times superior to those for multiple, i. e., divided into 3 or 5, SC administrations, and a single PO administration.
The in vitro postantibiotic effects (PAEs) of PZFX against Escherichia coli and Pseudomonas aeruginosa were examined. The PAE of PZFX was dependent on both the concentration and exposure time, but concentration was a more potent factor than exposure time.

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The in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, were compared with those of ceftazidime (CAZ), imipenem (IPM), gentamicin (GM), and ciprofloxacin (CPFX).
Pazufloxacin (PZFX), which is an active form of PZFX mesilate, showed a broader spectrum of activity than CAZ and GM and a spectrum similar to that of IPM and CPFX against grarnpositive and-negative bacteria. When tested against clinically isolated gram-positive bacteria, the MIC₉₀ value of PZFX against streptococci was 3.13 μg/ml, and inferior to that of IPM and CPFX. However, the MIC₉₀ values of PZFX against quinolone susceptible staphylococci and enterococci ranged from 0.2 to 6.25μg/ml and were superior to those of CAZ. The MIC₉₀ values against gram-negative bacteria, including cephem-resistant Enterobacteriaceae and CAZ-, IPM-, and GM-resistant Pseudomonas aeruginosa, ranged from 0.025 to 50 μg/ml. These values were superior to those of CAZ, IPM and GM for almost all gram-negative species.
At a concentration four times the MIC, the isolation frequencies of spontaneous mutants resistant to PZFX in various organisms ranged from < 3.1×10 ¹⁰ to 2.9 × 10⁸ The isolation frequencies of spontaneous mutants resistant to PZFX were lower than of spontaneous mutants resistant to CAZ in Enterobacter cloacae, Citrobacter, freundii and P. aeruginosa, which inducibly produce β-lactamase
PZFX was bactericidal above the MIC against Staphylococcus aureus, Escherichia coli and P. aeruginosa and its bactericidal activity in short periods was superior to that of CAZ and IPM. The bactericidal activity of PZFX in the log phase of S. aureus and P. aeruginosa, at drug concentrations equivalent to the serum Cmax of clinical doses in humans was superior to that of CAZ and GM. The PAE of PZFX in P. aeruginosa was superior to that of IPM and CAZ.
The therapeutic effect of PZFX mesilate against systemic infection caused by gram-positive and-negative bacteria including mutidrug-resistant strains in mice was about 1.45 to 496 fold superior to that of CAZ, and PZFX mesilate was also superior to CAZ against experimental respiratory tract infection and urinary tract infection, subcutaneous implanted disk infection, and CMC pouch infection.

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We investigated the pharmacokinetics of pazufloxacin mesilate (PZFX mesilate), the methanesulfonic acid salt of pazufloxacin (PZFX), after intravenous administration to experimental animals and obtained the following results.
1. The half-life of PZFX after a single intravenous administration of PZFX mesilate at a dose equivalent to 5 mg of PZFX/kg was 4.5 h in dogs, 1.0 h in rabbits, 0.88 h in rats, and 0.23 h in mice. No obvious differences among animal species were observed in serum levels of PZFX at 5 min after intravenous administration of PZFX mesilate, and the values were within the 4.77-6.83μg/ml range in all animals.
2. In rats, PZFX was rapidly distributed to various tissues except brain after a single intravenousadministration of PZFX mesilate. Particularly high distribution was found in the kidney, whilethe levels in other tissues were comparable to the serum levels. The PZFX concentrations in all tissues declined rapidly.
3. Urinary excretion rates of PZFX mesilate as the active form within 24 hours after intravenous administration were 44.7 % of the dose in mice, 74.3 % in rats, 54.9 % in rabbits, and 56.6% in dogs. The biliary excretion rate of PZFX mesilate as active form was 2.2% within 24 hours after intravenous administration in rats.
4. A dose-proportionality study was conducted with intravenous administration of PZFX mesilate at doses equivalent to 5 to 100 mg of PZFX/kg in rats. The AUCs were linearly proportional to the doses, and the urinary excretion rates were almost constant at these doses.
5. There were no significant differences in the serum levels or the urinary excretion rates after multiple administration twice daily for 6 days compared with the data after a single administration.
6. In rats with D-galactosamine-induced liver dysfunction the rate of decrease of the serum levels was slightly delayed, but there were no significant differences in the serum levels or the urinary excretion rates compared with those of normal rats. By contrast, in rats with HgCl₂-induced kidney dysfunction the serum levels were significantly increased and urinary excretion was significantly decreased.
7. No antimicrobially active compounds except PZFX were detected by bioautography in urine samples of mice, rats, rabbits, or dogs.

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We investigated the serum, urine, and tissue levels and the urinary excretion of pazufloxacin (PZFX) after intravenous injection of pazufloxacin mesilate (PZFX mesilate) at a dose of 10 mg (PZFX equivalent)/kg in mice and rats, and compared the results with the data for ciprofloxacin (CPFX) and ceftazidime (CAZ).
1. The serum levels of PZFX at 5 minutes after intravenous injection of PZFX mesilate to mice and rats were 8.29μg/ml and 10.0 μg/ml, respectively. They were lower than those of CAZ and higher than those of CPFX. In mice and rats, the half-life of PZFX after injection of PZFX mesilate was shorter than that of CPFX and longer than that of CAZ.
2. The urinary excretion of PZFX until 24 hours after intravenous injection of PZFX mesilate was 34.9 % in mice, and lower than that of CPFX and CAZ.
3. In rats, the urinary level and urinary excretion of PZFX until 1 hour after injection of PZFX mesilate was lower than that of CAZ and higher than that of CPFX. The urinary excretion of PZFX until 24 hours was 82.6 %. Its urinary excretion was lower than that of CAZ and higher than that of CPFX.
4. In rats, the tissue distribution of PZFX mesilate was better than that of CAZ and lower than that of CPFX.

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The metabolic fate of pazufloxacin mesilate, a injectable form of pazufloxacin (PZFX), was investigated in the urine of mice, rats, rabbits, and monkeys and bile from rats intravenously administered with pazufloxacin mesilate, or ¹⁴C-pazufloxacin mesilate, and human urine from volunteers in a phase I clinical study.
1. After intravenous administration of ¹⁴C-pazufloxacin mesilate (5 mg equivalent of PZFX/kg). a large portion of the radioactivity excreted in mouse urine was PZFX glucuronide, whereas the majority of radioactivity in rat urine was unchanged PZFX. Biliary excretion of unchanged PZFX played a minor role in ¹⁴C-pazufloxacin mesilate elimination in rats.
2. A glucose adduct metabolite, PZFXMl, was observed in the urine after intravenous administration of pazufloxacin mesilate to animals, in addition to PZFX glucuronide, the main metabolite of pazufloxacin mesilate. Oxidative metabolites, PZFXM2 and PZFXM3, were detected in rabbit and monkey urine. PZFXM2 and PZFXM3 excretion rates were higher in monkeys than in the other species.
3. In humans, most of the pazufloxacin mesilate (400 mg) administered was excreted in the urine as unchanged PZFX (94 %). PZFX glucuronide (5.7 %). and a little amounts of PZFXM2 and PZFXM3.
4. In humans, the glucuronidation rate of PZFX did not vary during repeated administration (300 mg, twice a day for 5 days) in comparision with the first dose.

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The serum level, distribution, and excretion of ¹⁴C-pazufloxacin mesilate (PZFX mesilate) were studied in rats and mice after single or repeated intravenous adiministation at a dose of 5 mg/kg.
1. Total clearance of ¹⁴C-PZFX mesilate in rats and mice was 1.03 1/h/kg and 1.21 1/h/kg, respectively, and distribution volume at steady state was 1.25 1/kg and 0.99 1/kg, respectively. Serum levels of radioactivity decreased biexponentially, with an elmination half life of 1.49 h and 1.91 h for rats and mice, respectively.
2. The main excretion route of the radioactivity was urinary excretion in both species, with excretion rates of 77 % and 68 % in rats and mice, respectively. The residual radioactivity was excreted in the feces. The excretion rate of radioactivity in bile in rats was 18%.
3. The tissue concentration of radioactivity was higher in kidney and liver, and widely distributed throughout the body, for example, in the submaxillary gland, spleen, lung, heart, bone marrow, lymph node, adrenal, pancreas and muscle, but not the central nervous systems.
4. After administration to lactating rats, relatively high levels of radioactivity were excreted into the milk (the concentration ratios to whole blood were 1.5-3.2). The concentration declined in parallel with the whole blood concentration.
5. When administered to pregnant rats, the radioactivity was transferred to fetuses (the concentration ratio to maternal plasma were 0.2-0.8) with slight delay in relation to the concentration change of maternal plasma.
6. Whole body autoradiograms of pregnant mice indicated that the radioactivity was widely distributed in maternal tissues, except the brain, spinal cord, and eyes, and that transfer to the fetus was delayed.

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The effects of pazufloxacin mesilate (PZFX mesilate), a new parenteral quinolone, on general behavior and the central nervous system (CNS) were investigated as part of general pharmacological studies. The following results were obtained.
1. PZFX mesilate at more than 200 mg/kg i. v. caused transient depression of the CNS as indicated by relaxation of body posture in the assessment of mouse behavior.
2. PZFX mesilate at lOO mg/kg i. v. displayed anti-reserpine activity in mice, but at 10-100 mg/kg i. v. had no effect on spontaneous locomotor activity, motor coordination, pentobarbital induced hypnosis, or convulsions in mice, passive avoidance response in rats, body temperature in rabbits, or the EEG in cats.
3. PZFX mesilate at up to 200 mg/kg i. v. failed to induce convulsions in 4-biphenylaceticacid (BPAA)-pretreated mice. At 10^-4 M it had no effect on γ-aminobutyric acid receptor binding in rat crude synaptic membrane either in the presence or absence of BPAA.

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The effects of pazufloxacin mesilate (PZFX mesilate), a new parenteral quinolone, on the respiratory and cardiovascular system, autonomic nervous system, digestive system, and function of other systems were investigated as part of general pharmacological studies, and the following results were obtained.
1. Respiratory and cardiovascular system: In anesthetized dogs, PZFX mesilate at 10-100 mg/kg i.v. produced a transient decrease in blood pressure and a transient increase or decrease in femoral blood flow. At 30 mg/kg or more, a decrease in heart rate, an increase in respiratory rate, and elevation of the T wave on the ECG were also observed. In anesthetized rabbits, it produced a transient increase in blood pressure at 10-100 mg/kg i.v.
2. Autonomic nervous system: PZFX mesilate at more than 10^-4g/ml inhibited acetylcholine-induced contraction of guinea pig ileum and epinephrine-induced relaxation of guinea pig trachea, and it enhanced the epinephrine-induced contraction of guinea pig vas deferens. Aggravation of epinephrine-induced hypertension in anesthetized dogs and mydriasis in mice was shown at 30 and 100 mg/kg i. v., respectively.
3. Gastrointestinal system: PZFX mesilate at more than 10^-4g/ml inhibited or enh anced the motility of isolated rabbit stomach, and inhibited that of the ileum and colon. It had no effect on intestinal propulsive motility in mice, or on gastric secretion and gastric mucosa in rats.
4. Function of other systems: PZFX mesilate at 100 mg/kg i.v. inhibited PSP excretion and increased urinary K⁺ excretion in rats. At more than 10^-4g/ml, it enhanced or inhibited the spontaneous motility of isolated rat uterus, and inhibited platelet aggregation in rabbits. Vascular-permeability-enhancing activity in rats and a weak hemolyzing effect on rabbit washed erythrocytes was shown at 2×10^-3 and 3×10^-3g/ml, respectively.

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A phase I clinical study of pazufloxacin mesilate (PZFX) was conducted in 52 healthy male adults. The single-dose (drip infusion over 30min) study was started at 50mg, and serially increased to 100, 200, 400, and 500mg.
The multiple-dose study was carried out at doses of 300 and 500mg twice daily and 500 mg 3 times daily, for 5 days. The effect of drip infusion time and combined dosing with probenecid was assessed, and the following results were obtained.
Slightly increased NAG was observed in 2 cases in the 500mg single-and multiple-dose study. No other abnormal subjective or objective findings, physical findings, electrocardiographic findings, or laboratory test values were detected.
Dose-dependent changes were observed in serum levels during the single-dose study with 50, 100, 200, 400, and 500mg of PZFX. The maximum serum levels were observed at 30min, at the end of drip infusion, and were 1.28, 2.68, 4.61, 9.93, and 11.0μg/ml, respectively, with half-lives in serum of 1.74-1.88 hours. Cmax and AUC were proportional to the doses. Urinary excretion rates showed little change with increasing dose, and were 89.5-93.9% at 24hours after administration. The serum levels reached a plateau on day 1 in the multiple-dose study, and no accumlation was observed on the basis of urinary excretion rates. Comparison of 30-and 60-min drip infusion time revealed that the maximum serum levels for 60min was decreased to 80% of the maximum level for 30min. No safety problems were observed with the 1, 000 mg single-dose. Combination with probenecid increased the half-life in blood and decreased the urinary excretion rates. This shows that the mechanism of urinary excretion of PZFX is related to glomerular filtration and tubular absorption.
Thus, PZFX appears to be free of safety problems, and in view of its pharmacokinetics and antimicrobial activity against various organisms, a clinical trials seems warranted.

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The clinical efficacy, safety, and usefulness of intravenously infused pazufloxacin (PZFX), a pyridonecarboxylic acid derivative, were evaluated for treatment of moderate to severe respiratory tract infections. In this study, patients were treated with PZFX by intravenous drip infusion at a dose of 300 or 500 mg, twice or three times a day for 3 to 14 days. The results obtained are as follows:
1. Among the 278 patients enrolled, 241 cases, 253 cases, and 236 cases were adopted to analyze efficacy, safety, and usefulness, respectively.
2. The clinical efficacy rate in respiratory tract infections was 75.1%(181/241) overall, 76.1%(67/88) for chronic respiratory tract infections, and 75.7 %(109/144) for pneumonia/lung suppuration. The clinical efficacy rate in poor responders to other antimicrobial agents, was 63.3%(38/60). The clinical efficacy rate classified by daily dose was 74.2%(49/66) in the 600 mg dosing group and 74.7%(124/166) in the 1000 mg dosing group. The causative-organism elimination rate was 69.2%(72/104) overall.
3. Side effects were noted in 11 cases (4.0%) and consisted of central nervous system disorders in 3 cases, allergy symptoms in 2 cases, gastrointestinal symptoms in 5 cases, and dry mouth in 1 case. Abnormal laboratory findings were noted in 36 cases (14.3%) mainly consisting of serum transaminase elevation in 16 cases and eosinophilia in 12 cases.
4. The usefulness rate for respiratory tract infections was 72.9%(172/236) overall. The usefulness rate according to daily dose was 71.4%(45/63) in the 600 mg dosing group and 72.6%(119/164) in the 1000 mg dosing group.
Based on the above findings, intravenously infused PZFX seems to be effective, safe, and useful for the treatment of patients with moderate to severe respiratory tract infections.

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The antimicrobial activity, penetration, and clinical efficacy of pazufloxacin mesilate, a new injectable fluoroquinolone derivative, were evaluated tentatively. We obtained some knowledge of pazufloxacin mesilate and these were reported here.
The results were as follows.
1) Antimicrobial activity
The antimicrobial activity of pazufloxacin (PZFX), the active form of pazufloxacin mesilate was determined against 115 strains of clinical isolates. The 90% minimum inhibitory concentration (MIC₉₀) of PZFX was 25μg/ml for Staphylococcus aureus, 3.13μg/ml for Streptococcus pneumoniae, 0.05μg/ml for Escherichia coli, 0.05μg/ml for Klehsiella pneumoniae, 0.05μg/ml for Haemophilus spp., and 6.25μg/ml for Pseudomonas aeruginosa.
2) Pharmacokinetics
When 500mg of pazufloxacin mesilate was intravenously administered to a patient with diffuse panbronchiolitis twice daily for 11 days, the range of concentrations of PZFX in serum was 3.88-17.04μg/ml. The peak concentrations of PZFX in sputum and saliva were 13.50 μg/g and 4.88μg/ml, respectively, on day 1, 6.70 μ/g and 4.14μg/ml on day 3, and 6.92 μg/g and 4.72μg/ml on day 5, and the penetration of PZFX from serum to sputum and saliva (sputum or saliva/serum) was 64%-97% and 16%-28%, respectively.
3) Clinical efficacy
The clinical effect was evaluated in 11 patients including 4 with bacterial pneumonia, 1 with pulmonary abscess, 3 with secondary infection to chronic respiratory disease, 1 with acute bacterial exacerbation of chronic bronchitis, 1 with diffuse panbronchiolitis, and 1 with mycoplasmal pneumonia.
After excluding 1 case with an ineligible disease (mycoplasmal pneumonia), the efficacy rate was 100%, reflecting a wide antimicrobial spectrum and favorable penetrations. Moreover, body temperature, sputum property and dyspnea improved rapidly. Except for mild eosinophilia, which occurred in 2 patients, no side effects or abnormal laboratory findings were observed.
Based on the above, it is concluded that pazufloxacin mesilate is one of the most effective injectable antimicrobial agents for the treatment of patients with respiratory tract infections, with no severe side effects.

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The pharmacokinetics of pazufloxacin mesilate (PZFX mesilate), a newly developed quinolone antimicrobial agent, were investigated in the elderly. The seven patients (71-88 years old) were classified according to creatinine clearance (Ccr) values into three groups: Group I (n=2), Ccr≥60ml/min, Group II (n=2), Ccr 20-60ml/min, and Group El (n=3), Ccr≤20 ml/min. A 300mg dose of pazufloxacin mesilate given to each patient by 30 minute intravenous infusion. The drug concentrations in serum and urine collected from the patients were determined by HPLC. The results were as follows:
1. Cmax in each group was reached when the infusion was completed.
2. The drug concentrations in serum decreased more slowly in patients with serious renal dysfunction than in those with mild or moderate renal dysfunction.
3. T_1/2 grew longer in proportion to the severity of the renal dysfunction: Group I, 2.3-2.4 hr; Group II, 4.6-4.7 hr; Group III, 12.1-18.3hr.
4. AUC also increased according to the severity of the renal dysfunction: Group I, 12.3-17.8μg · h/ml; Group II, 38.5-53.7μg · h/ml; Group III, 94.2-148.2μg · h/ml.
5. The urinary recovery rates up to 24 hours of PZFX mesilate decreased in proportion to the severity of the renal dysfunction: the rates in Group I, II, and III were 80.7-92.8%, 60.9-63.6%, and 12.2-28.6%, respectively.

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The clinical efficacy, safety, and usefulness of pazufloxacin mesilate, a new parenteral quinolone, in complicated urinary tract infections were evaluated as a phase II study.
As a rule, patients were intravenously infused with 300mg twice daily, or 500mg twice or three times daily, for 5 consecutive days. The following results were obtained.
1. Of the 179 patients infused, 150 were evaluated for clinical efficacy, 164 for safety, and 139 for usefulness, according to the criteria proposed by the Japanese UTI Committee.
2. The overall clinical efficacy rate was 78.7% in all 150 cases, 75.9% in the 58 cases with complicated pyelonephritis, and 80.4% in the 92 cases with complicated cystitis.
3. The overall clinical efficacy rate was 81.6% at the 300mg twice daily dosage, and 77.0% at the 500mg twice daily dosage.
4. The clinical efficacy rate evaluated by doctor was 81.3% in the 150 cases.
5. The overall bacteriological eradication rate was 85.9%, 79.3% for gram-positive bacteria and 91.9% for gram-negative bacteria.
6. Two adverse events were experienced in 179 patients and were mild to moderate in degree. Thirteen events of abnormal changes in laboratory findings were observed in 163 patients and were mild to moderate in degree. The incidence of adverse reactions and abnormal changes in laboratory findings was 1.1% and 8.0%, respectively.
7. From the above findings, we concluded that pazufloxacin mesilate is useful in the treatment of complicated urinary tract infections at the dosages of 600mg to 1500mg daily.

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Pazufloxacin mesilate (PZFX mesilate), a newly developed intravenous fluoroquinolone antibacterial agent, was evaluated clinically against surgical infection and its tissue concentrations, and the following results were obtained.
PZFX mesilate (300 mg or 500 mg) was intravenously administered 2 or 3 times daily for 3-14 days to patients with surgical infections.
The clinical efficacy rates were 78.3%(18/23) for intra-abdominal infection, 86.7%(13/15) for biliary tract infection, 73.7%(14/19) for wound infection, 86.7%(13/15) for postoperative pneumonia, 2/2 for sepsis, and 1/1 for cellulitis, osteomyelitis, and periproctal abscess. The clinical efficacy rate for Pseudomonas aeruginosa mixed infection was 80.0%(12/15).
None of the patients showed side effects. Abnormal laboratory data were observed in 10 cases (12.5%), and the major findings were elevated transaminases, eosinophilia, and decreased leukocyte counts.
PZFX mesilate (300mg or 500mg) was intravenously administered to 10 patients scheduled to undergo cholecystectomy. PZFX showed good tissue penetration with tissue concentrations of 0.54-13.6μg/g in the gallbladder, <0.5-212μg/ml in bile in the gallbladder, and 5.77-39.5μg/ml in bile in the bile duct, compared with corresponding serum concentrations of 0.45-11.8μg/ml.
The peak bile concentration in patients after insertion of a PTCD-tube or T-tube ranged from 5.47-56.4μg/ml and was about 4 times higher than the corresponding serum concentrations.
The concentration of glucuronic-conjugated PZFX in bile in the gallbladder and bile duct was the same as or lower than that of unchanged PZFX.
The peak PZFX concentrations in ascitic fluid, pleural effusion, and sputum, with corresponding serum concentrations in parenthesis, were 1.87-2.40μg/ml (1.74-6.30μg/ml), 1.43μg/ml (0.34μg/ml), and 0.87-6.24μg/g (1.89-10.5μg/ml), respectively.
These results suggest that intravenous PXFX is useful for the treatment of surgical infection.

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The clinical efficacy of pazufloxacin mesilate, a new parenteral fluoroquinolone, was evaluated and following results were obtained.
1) A drip infusion of 500 mg over 30 minutes was given to five patients scheduled for radical hysterectomy who agreed to participate in this study. Both serum levels and retroperitoneal exudate levels were periodically measured by high-performance liquid chromatography (detection limit: 0.01 μg/ml).
Serum levels and retroperitoneal exudate levels peaked at 15 to 30 minutes and 1.5 to 2.5 hours, respectively, after pazufloxacin mesilate administration. The mean maximum serum levels and retroperioneal exudate levels were 20.89 μg/ml and 6.98 μg/ml, respectively.
2) A daily dose of 1000 mg or 600 mg (in 2 divided doses) was given to pelvic peritonitis patients. Clinical efficacy was evaluated as excellent in one patient and good in 4 patients. Seven species, 8 strains, were isolated from 5 patients, and 7 of those strains were eradicated. No adverse reactions or abnornal laboratory findings were observed in these patients. The above results show that pazufloxacin mesilate is useful for the treatment of obstetric and gynecological infection at daily doses of 600 mg or 1000 mg.

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