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The pharmacokinetics of cefotaxime after intramuscular injection and intravenous infusion were determined. The mean peak serum level after the 500-mg intramuscular dose was 11.7 ,ug/ml, and it was 20.5 ,ug/ml after a 1,000-mg dose.The serum half-life was 1.2 and 1.3 h, respectively for the two doses. The apparent fractional volumes of distribution of 32 and 37 liters were All subjects were judged healthy on the basis of history, physical examinations, chemistry profile (SMA 12/60; Technicon), complete blood count, urinalysis, and creatinine clearance. Subjects with known sensitivity to penicillins or cephalosporins were excluded. Intramuscular injection study. Fourteen subjects were divided into two groups. Group A (seven subjects) received an intramuscular injection of 500 mg of cefotaxime, followed 1 week later by a 1,000-mg injection. Group B (seven subjects) received 1,000 mg followed 1 week later by a 500-mg dose. Blood samples were obtained at 0, 15, 30, 45, 60, 90, 120, 180, 240, and 360 min after the injection. Urine samples were collected immediately before injection and at 0 to 2, 2 to 4, 4 to 6, 6 to 12, and 12 to 24 h after the drug had been administered. Blood samples were allowed to clot at room temperature and centrifuged, and the serum was decanted within 1 h of collection. Each serum and urine sample was divided in aliquots, immediately frozen, and stored at -20°C until assay. Cefotaxime in urine, serum, and phosphate buffer was found to be stable for 3 months at -20°C at concentrations of 50 ,ug/ml.Intravenous infusion study. Ten healthy males were selected for this study. Each received 1,000 mg of cefotaxime infused intravenously through a small-bore needle over a 30-min period. Blood samples were drawn before infusion and at 30, 45, 60, 75, 90, 120, 180, and 240 min after the start of the infusion. Urine samples were collected before infusion of the agent and at intervals of 0 to 2, 2 to 4, 4 to 6, and 12 to 24 h. Samples were processed as detailed above.Assays. Cefotaxime was assayed by the agar well diffusion technique, using antibiotic medium no. 2 (Difco Laboratories) as previously described (2,

I The effects of age and sex on the disposition of clobazam (CBZ), a 1 ,5-benzodiazepine derivative, were evaluated in a series of 29 healthy volunteers aged 18 to 72 years, who ingested single 20 mg oral doses. CBZ kinetics were determined from multiple plasma concentrations measured during 7 days after the dose. 2 CBZ was rapidly absorbed, with peak levels reached an average of 1.5 h after dosing (range 0.5-2.5 h). Mean absorption half-life was 19.7 min. Absorption kinetics were not influenced by age or sex. 3 Elimination half-life ranged from 11 to 77 h, and was significantly longer in elderly v young males (48 v 17 h, P < 0.01). In women, half-life also increased with age, but differences between young and elderly women were less striking (31 v 49 h, P < 0.05). 4 Volume of distribution (Vd) was influenced by age and sex. Vd became larger with age regardless of sex, and within each age group was larger in women than in men. Total clearance was unrelated to age in women, but declined significantly with age in men (P < 0.01). 5 The mean free fraction for CBZ in plasma was 11.5% (range 8.6-15.0%), and tended to increase with age, partly due to a significant age-related decline in plasma albumin concentration (r = -0.68, P < 0.001). Correction of Vd and clearance for individual differences in binding did not alter their relation to age and sex. 6 As in the case of other benzodiazepines biotransformed by oxidative pathways, the capacity for N-demethylation of CBZ declines with age in men, but age has a minimal effect on CBZ clearance in women.

The kinetics of single 20-mg oral doses of clobazam was determined on two occasions in 12 healthy male volunteers. Clobazam was given in the fasting state on one occasion and following a standard breakfast on another. Compared with the fasting state, administration of clobazam with food reduced mean peak plasma concentrations (465 vs. 333 ng/ml, P less than 0.01), and prolonged the time to reach peak concentration (1.7 vs. 2.5 hours after dosage, P less than 0.1). Total area under the curve nor the extent of formation of desmethylclobazam, the major metabolite. Clobazam AUC and elimination half-life each were highly correlated within subjects between the two trials (r = 0.97 and 0.95, respectively). Thus, administration of clobazam with food slows the rate of clobazam absorption but does not alter the completeness of absorption. The rate of drug elimination is highly replicable upon repeated administration clobazam to the same individual.