Pharmacokinetics of cefotaxime in sheep.

Five healthy adult Merino ewes were each given 2 g of cefotaxime by the IV, IM, and subcutaneous (SC) routes. The serial plasma samples collected after each treatment were analyzed for cefotaxime by a new high-pressure liquid chromatographic method. Plasma concentration time profiles were characterized by a linear 2-compartment model after IV administration and the following mean values (+/- SD) were found: biological half-life, 23 +/- 8 minutes; apparent volume of distribution, 5.5 +/- 1.3 L; plasma clearance, 0.37 +/- 0.09 L/min; elimination rate constant, 0.066 +/- 0.014 minute-1; rate of diffusion into tissue, 0.013 +/- 0.013 minute-1; and out of tissue, 0.035 +/- 0.017 minute-1. Plasma cefotaxime concentrations in the ewes given the drug by the IV, IM, and SC routes were 113 +/- 32, 71 +/- 20, and 38 +/- 11 micrograms/ml, respectively, at 15 minutes; 2.31 +/- 0.82, 11.3 +/- 6.6, and 16.4 +/- 3.7 micrograms/ml at 120 minutes; and 1.05 +/- 1.22, 9.3 +/- 5.2, and 14.9 +/- 1.27 micrograms/ml at 150 minutes. After cefotaxime was given SC and IM, plasma values were higher for a longer time than they were after the drug was given IV, probably due to a slower release of drug from the former injection sites.