Cefotaxime kinetics after intravenous and intramuscular injection of single and multiple doses.

The kinetics of cefotaxime, a cephalosporin with an unusually broad antibacterial spectrum, were examined in humans after intravenous bolus injection, intravenous infusion every 6 hr for 14 days, and intramuscular injection every 8 hr for 10 days. Mean peak serum level after bolus injection of 500 mg was 37.9 microgram/ml; after 1 gm, 102.4 microgram/ml; and after 2 gm, 214.1 microgram/ml. The half-life (t1/2) was 1 hr for the 3 doses. Total serum clearance was the same for all doses. Overall excretion was 50% to 60%; part of the drug was excreted as the desacetyl derivative. After multiple intravenous infusion the elimination rate constants and t1/2 were the same on days 1 and 15. Assayable levels were present on all days 5 min before injection of a dose. Multiple intramuscular injections of 500 mg produced serum levels of 9.2 to 11.9 microgram/ml. The t1/2 was 0.93 hr. Mean serum levels at 8 hr ranged from 0.08 to 0.55 microgram/ml. Serum levels produced by intravenous infusion or intramuscular injection were inhibitory for most (90%) aerobic gram-positive and gram-negative organisms susceptible to cefotaxime.

Comparative efficacy of cefotaxime and cefazolin as prophylaxis against infections following elective hysterectomy.

The safety and efficacy of cefotaxime and cefazolin as prophylaxis against posthysterectomy infections were compared in a prospective, randomized study. A total of 118 women undergoing elective vaginal or abdominal hysterectomy were randomly assigned to receive either (1) cefotaxime perioperatively, (2) cefotaxime perioperatively and 24 hours postoperatively, or (3) cefazolin perioperatively and 24 hours postoperatively. In all regimens, the initial antibiotic dose was given intramuscularly and subsequent doses were given intravenously. No postoperative pelvic or wound infections developed in patients in any of the three study groups during the hospital stay or in the 30-day follow-up period. No side effects or changes in laboratory test values attributable to the antibiotics were noted. The results of the study indicate that (1) standard one-day regimens of cefotaxime and cefazolin are equally safe and effective as prophylaxis against posthysterectomy infections, and (2) a brief, three-dose perioperative course of cefotaxime is as effective as a standard one-day regimen of either cefotaxime or cefazolin and has the advantages of reduced cost and greater convenience.

Pharmacokinetics of cefotaxime.

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 micrograms/ml, and it was 20.5 micrograms/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 not significantly different for the two doses, and the fractional serum clearance was approximately 315 ml/min per 1.73 m2 for both doses. The mean peak serum level after 1,000 mg administered by intravenous infusion over 30 min was 41.1 micrograms/ml. The half-life was 1.13 h, apparent volume of distribution was 33 liters, serum clearance 341 ml/min per 1.73 m2, and renal clearance was 130 ml/min per 1.73 m2. The pharmacology of cefotaxime is similar to the pharmacology of other cephalosporin antibiotics, but the low inhibitory levels which it has against gram-positive and gram-negative bacteria suggest that lower dosage regimens should be possible.