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

Abstract

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