Pharmacokinetic Study of Cefotaxime (CTX) in Dogs

Cefotaxime (CTX) was injected either intravenously or intramuscularly in dogs, and its pharmacokinetics in plasma and urine were determined with the use of HPLC assay. Cephalothin (CET) was administered in a similar manner as a reference agent. While both CTX and CET rapidly disappeared from plasma after intravenous injection, the half-life of CET was approximately 2.5 times shorter than that of CTX. Both drugs were deacetylated, and desacetyl-CTX and desacetyl-CET appeared in plasma. Both drugs were rapidly excreted into urine either in unchanged or deacetylated form, the sum of which accounted for 77 % and 63 % of the CTX and CET dose, respectively. The ratio of the amount of unchanged drug over that of deacetylated drug in the urine was 1:1 for CTX and 1:2 for CET. When CTX and CET were intramuscularly injected, the plasma levels of CTX and CET reached a maximum 30 min and 15 min after injection, respectively, followed by a rapid decline. The pattern of urinary CTX excretion was similar after i.m. and i.v. injections. In contrast, the amount of desacetyl-CET in the urine was larger after i.m. than i.v. injections. CTX metabolites other than desacetyl-CTX (M2 and M3) that were also assayed by HPLC accounted for only 2-4 % of the dose of CTX in the urine, but were below detectable levels in this plasma.