We studied the pharmacokinetics of biapenem (BIPM), a new carbapenem antibiotic, for comparison with imipenem/cilastatin (IPM/CS) by the cross-over method.A BIPM dose of 300mg and 500mg/500mg of IPM/CS were administered to six healthy volunteers by intravenus drip infusion. The plasma and urine concentrations were measured by HPLC assay together with a bioassay. The correlations of BIPM and IPM plasma were 0.986 and 0.979;urine 0.992 and 0.995. There was a high correlation between bioassay and HPLC measurement in this study.The plasma concentrations (C_max) of IPM/CS, panipnemlbetamipron (PAPM/BP) and meropenem (MEPM) were found to be higher than that of BIPM, but there was no difference in the plasma half-life beta phase (T_1/2β) in the terms of elimination phase between the 4 drugs.The urinary excretion rates for BIPM, IPM/CS, PAPM/BP and MEPM were 60.0%, 69.8%, 37.3% and 64.5%, respectively. These results suggest that the pharmacokinetics and stability of BIPM are nearly the same as that of IPM/CS.No side effects or abnormal laboratory findings were observed in this investigation.

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We randomly sampled inpatients with respiratory infections who were treated with injectable antibiotics in 1993-1994.Patients were classified according to treatment with imipenem/cilastatin (IPM/CS) versus cephem drugs as the first choice.The method of selection of antimicrobial drugs was evaluated from the socioeconomic aspect.A cost effectiveness analysis was performed using data from 106 patients (40 in the IPM/CS therapy group and 66 in the cephem therapy group) in whom evaluation was possible.According to the severity of infection, the cost-effectiveness ratio (C/E) derived from the cost per patient was evaluated.In “mild-moderate” infections, the C/E was-2.465 in the IPM/CS therapy group and-2.320 in the cephem therapy group.In “severe” infections, the WE was-2.424 in the IPM/CS therapy group and-2.305 in the cephem therapy group.Thus, IPM/CS was more cost effective than cephem.An increment analysis was performed to determine the cost savings due to shortening the treatment duration by 1 day (ΔC/ΔE). The ΔC/ΔE was-1.848 for “mild-inoderate” infections and-1.849 for “severe” infections. These results showed that the use of IPM/CS not only shortens the treatment duration but also decreases the cost per day by 18, 480 yen in “mild-moderate” infections and by 18, 490 yen in “severe cases.” ΔC/ΔE according to the presence or absence of underlying respiratory diseases was-1.051 for cases without (“absence”) and-1.848 for cases with such diseases (“presence”). The use of IPM/CS was more cost effective in patients with than in those without underlying diseases. IPM/CS was also more cost effective than therapy.In the cephem group, the inital drug was changed to other drugs because of clinical effects in 9 of the 66 patients;the switch was to IPM/CS in 6 of these 9 patients.In the IPM/CS group, the initial drug was changed to cephem drugs in only 1 case.Ineffectiveness of the first choice drug results in increased medical costs. Therefore, the use of drugs with marked antimicrobial action such as IPMJCS in the early stage of infection shortens the treatment period, increases the benefit to inpatients, and reduces medical costs.

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Linoleic acid, oleic acid, camellia oil, purified camellia oil, olive oil, jojoba oil, squalane and liquid paraffin were examined for inhibitory activity against Staphylococcus aureus FDA 209 P. Standard solutions of oils at 80μg/ml were serially diluted two-fold with additional broth.An overnight culture was added to each dilution to give approximately 1.0×10⁷ colony-forming units per ml (cfulml). The inhibitory activity of samples on growth was monitored turbidimetrically. The results showed that linoleic acid, oleic acid and camellia oil had strong inhibitory activity against S.aureus FDA 209 P.Both purified camellia oil and olive oil showed relatively low inhibitory activity against S.aureus FDA 209 P.The 50% inhibtory dose (ID 50) of purified camellia oil was compared with that of other fatty acids and oils.A comparison of the ID 50 of purified camellia oil with those of other fatty acids and oils revealed that purified camellia oil exerted stronger inhibitory activity than that of olive oil.Jojoba oil, squalane and liquid paraffin showed. no inhibitory activity against S.aureus FDA 209 P at the concentrations tested.The results suggest the purified camellia oil and olive oil are potentially useful skin care products for skin affected by atopic dermatitis.

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Rokitamycin (RKM) was investigated in terms of bactericidal activity and PAE against clinically isolated bacteria consisting of one strain of Staphylococcus aureus, one strain of Streptococcus pyogenes and three strains of Streptococcus pneumoniae in comparison with reference antibiotics, clan ithromycin (CAM), erythromycin (EM) and cefditoren (CDTR).RKM exhibited an antibacterial potency which was almost the same as that of EM against S.aureus and S.pyogenes, and superior to the other three antibiotics against penicillin-resistant S.pneumoniae.According to our investigation of bactericidal activity, RKM showed the strongest activity against the three kinds of bacteria tested.In addition, RKM showed PAE, which was somewhat shorter than those of CAM and EM against S.aureus, but almost as long against S.pneumoniae and longer against S.pyogenes, and longer than that of CDTR against all the strains of bacteria tested.In conclusion, RKM is evaluable as a highly useful antibiotic for the treatment of respiratory tract infections because of its excellent antibacterial potency against gram-positive bacteria including penicillin-resistant S.pneumoniae together, with its strong bactericidal activity and relatively long PAE among members of the new macrolide antibiotic family.

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Sporadic case reports concerning the hypoglycemia caused by new quinolones have appeared in western countries as well as in Japan. In this study, oral glucose tolerance tests (OGTT) with 75g of glucose were conducted before and after the administration of enoxacin 200mg tid.for 3-5 days to 5 subjects with non-diabetic chronic renal insufficiency;in addition transitions in the levels of blood glucose, insulin, C-peptide, glucagon, growth hormone and cortisol were estimated. The results of the OGTT and fasting blood glucose levels were not significantly altered in these subjects after treatment.The mean blood insulin level was, however, elevated from 6.4μU/ml to 9.6μU/ml, while the mean insulin level 30 minutes after the oral administration of glucose on the OGTTs revealed a lowering tendency with enoxacin treatment.These results suggest that enoxacin enhances insulin secretion.Further more, there is also a possibility that enoxacin potentiates responsiveness to insulin in peripheral tissues or in the liver.

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Many fluoroquinolones developed in Japan have good biliary transfer, and are put to clinical use for biliary tract infection.However, it is not regulated what kind of fluoroquinolone are suitable for chemotherapy of biliary tract infection.In this study, we examined biliary and urinary concentration of sparfloxacin (SPFX), pazufloxacin (PZFX), and DU-6859a, a new fluoroquinolone, and the rate of un-changed fluoroquinolones and their glucuronides in three kinds of hyperbilirubinemic rats.Where there was obstructive jaundice, each unchanged fluoroquinolone was transferred to bile at a lower rate than the control, but was excreted in the urine at a higher rate than the control.Both PZFX and DU-6859a was transferred to bile at the higher rate than SPFX.In EHBR, the excretion rate of both unchanged fluoro-quinolones and the associated glucuronides into bile decreased remarkably compared with the control, but the excretion rate of the associated glucuronides into urine increased compared with rats with obstructive jaundice, where whole UDP-glucuronic acid levels decreased.In the Gunn rat, each excretion rates into bile varied according to the kind of fluoroquinolone, due to varying affinities for plasma protein.PZFX and DU-6859a, which have a low binding rate to plasma protein, were excreted in bile at a higher level than SPFX.A proportion of fluoroquinolones may be metabolised by different isoenzymes of UDP-glucuronosyltransferase from bilirubin, because there were glucuronides of PZFX and DU-6859a in the bile of Gunn rats.Thus, the use of a fluoroquinolone as an antibacterial agent in patients with biliary tract infection may be affected by the grade of jaundice and level of liver dysfunction in these patients.

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We determined the in vitro bactericidal activity of cefditoren (CDTR) against Haemophilus influenzae with the simulation of human tonisilla palatina concentrations after oral administration of cefditoren pivoxil (CDTR-PI).The results were as follows.
1.The peak tonsilla palatina concentration of CDTR was about 0.2μg/ml when analyzed following a pharmacokinetic model after oral administration of CDTR-PI at 200mg.
2.CDTR showed bactericidal activity against H. influenzae PRC 2 and the number of viable cells markedly decreased about 2 log after 6 hours.

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