We carried out an examination of the therapeutic effects of Cefotiam (CTM) against uterineinfectious diseases by using a rabbit experimental model of intra-uterine infection. Cefazolin (CEZ) was used as the standard antibiotic in each test.
1) MIC of CTM and CEZ against 10⁶cells/ml of E. coli PYO-252 strain, which were inoculated into rabbit uteri, were 0.1μg/ml and 3.1μg/ml, respectively.
2) Plasma level of both antibiotic after a single intravenous injection quickly fell. However, 60 minutes after injection, the concentration of CEZ in plasma was a little higher than that of CTM. The concentration of CEZ in the uterine tissue was 3 to 5 times that of CTM.
3) In vivo therapeutic examination was performed. By the injection of 60mg/kg/day of CTM for 4 days, the inoculated E. coli disappeared and almost no pathological findings were recognized in the inoculated uterine horn. The minimal effective dose measured by the disappearance of E. coli was 60mg/kg/day of CEZ and 30 mg/kg/day of CTM. Thus CTM was as effective as CEZ at half the dose.
Accordingly, it is strongly suggested that CTM has a use in the therapy of the uterine infectious diseases.

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Choledocal bile was collected every 30 or 60 minutes from 14 patients under T-tube drainage and 2 patients under PTC drainage, to study how antibiotics penetrate into biliary system. Ceftazidime (CAZ) and cefazolin (CEZ) were used for this study. Three groups were set up for each drug;(a) bolus injection of 1g intravenously (1g iv), (b) bolus injection of 2g intravenously (2g iv), (c) drip infusion of 2g intravenously for 60 minutes (2g div). The concentration of antibiotics was measured by the thin layer disc method.
The peak concentration and the recovery rate in bile was as follows (1) CAZ 1g iv (n=9) 27.6μg/ml, 0.39%, (2) CAZ 2g iv (n=4) 36.7μg/ml, 0.30%, (3) CAZ 2g div (n=5) 37.6μg/ml, 0.30%, (4) CEZ 1g iv (n=8) 14.3μg/ml, 0.07%, (5) CEZ 2g iv (n=7) 34.6μg/ml, 0.07%, (6) CEZ 2g div (n=5) 12.5μg/ml, 0.03%. That is, the more the dose of antibiotics was, the higher the concentration of antibiotics in bile was. Though the result of CAZ 2g iv was similar to that of CAZ 2g div, the result of CEZ 2g iv was evidently better than that of CEZ 2g div. On timeconcentration curve, the peak of CEZ was sharp, but that of CAZ showed plateau for 5 to 6 hours.
So, it was suggested that CAZ may be administered 1g or 2g, twice a day and CEZ should be administered 2g, 3 times a day. On the other hand, it was suspected that bolus injection might be superior to drip infusion, for the penetration of antibiotics into bile.

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The effect of β-lactam antibiotics on the Sub-Minimum inhibitory concentration (Sub-MIC) in human serum and in various animal serums were studied.
In nutrient broth (NB) and in various animal serums, piperacillin (PIPC), cefoperazone (CPZ) and cefbuperazone (T-1982) showed bacteristatic or bactericidal activity, and difference in bactericidal activity was observed among species of animal. PIPC provided stronger activity in rabbit serum and in human serum than in NB. This was supported by the observation on phase contrast micrographs and electron micrographs.
Carbenicillin (CBPC), cefazolin (CEZ) and cefmetazole (CMZ) slightly inhibited the growth of bacteria in NB, but they hardly showed bactericidal activity in the serums.
Bactericidal activity of any of above β-lactam antibiotics in heat-treated serum was inferior to that in fresh serum, which suggested the relevancy of the complement etc.

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The pharmacokinetics of cefpiramide (CPM), a new parenteral semisynthetic cephalosporin derivative, were studied in 6 healthy adult volunteers and 31 patients with impaired renal function after the administration of a single 500-mg dose intravenously. CPM concentrations in serum and urine were determined by the agar well method with Escherichia coli NIHJ as a test organism and sensitive test agar as a test medium. Endogenous creatinine clearance was used as an indicator of renal function. Pharmacokinetic parameters were estimated from a two-compartment open model, using a NONLIN nonlinear regression program. The serum levels in patients with renal impairment were slightly higher than those in healthy volunteers for varying periods from 30min. to 24hr. postdrug. The mean serum half-life during β-phase, 4.06hr. in normal subjects, were slightly prolonged in patients with impaired renal function; the prolongation, however, was not remarkable. The mean 24-hr. urinary recovery rate of CPM was 21.5% in normal subjects and decreased with decreasing renal function to 0.6% in 10 hemodialysis patients. There was no significant relationship between the creatinine clearance and pharmacokinetic parameters obtained from the serum concentration-time curve; serum half-life during β-phase, elimination rate constant, distribution volume or area under the serum concentration curve. On the contrary, the urinary recovery rate and renal clearance of the drug were decreased with a corresponding diminution of renal function. The mean serum half-life during β-phase was not shortened by hemodialysis. These results suggest that injected CPM is mainly excreted by other organs than the kidney, probably the liver.

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