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 µg/ml; after 1 gm, 102.4 µg/ml; and after 2 gm, 214.1 µg/ml. The half-life (t½) 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 t½ 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 µg/ml. The t½ was 0.93 hr. Mean serum levels at 8 hr ranged from 0.08 to 0.55 µg/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. Clinical Pharmacology and Therapeutics (1980) 27, 677–685; doi:10.1038/clpt.1980.96