PHARMACOKINETICS OF CEFEPIME AND COMPARISON WITH THOSE OF CEFTIOFUR IN HORSES

Objective-To determine pharmacokinetics of IV, IM, and oral administra tion of cefepime in horses and to compare pharmacokinetics of IM admin istration of cefepime with those of ceftiofur sodium. Animals-6 clinic ally normal adult horses. Procedure-Horses received 3 doses of cefepim e (11 mg/kg of body weight, PO; 2.2 mg/kg, IV; and 2.2 mg/kg, IM) and 1 dose of ceftiofur (2.2 mg/kg, IM). Two horses also received L-argini ne, PO and IV, at doses identical to those contained in the cefepime d i-hydrochloride-L-arginine preparations previously administered. Blood samples were collected for 24 hours after administration of cefepime or ceftiofur and were assayed for cefepime and ceftiofur concentration s. Results-Pharmacokinetic analysis of disposition data indicated that IV administration data were best described by a 2-compartment open mo del, whereas IM administration data were best described by a 1-compart ment absorption model. Median elimination half-life and volume of dist ribution after IV administration of cefepime were 125.7 minutes and 22 5 ml/kg, respectively. After IM administration of cefepime, mean maxim al plasma concentration of (8.13 mu g/ml) was reached at a mean time o f 80 minutes. Absorption of cefepime after IM administration was compl ete, with a median bioavailability of 1.11. intramuscular administrati on of ceftiofur resulted in similar mean maximal plasma concentration (7.98 mu g/ml) and mean time to this concentration (82 minutes). Cefep ime was not detected in samples collected after oral administration. A dverse effects consisting principally of gastrointestinal disturbances were observed after oral and IM administration of cefepime and after 1 IM administration of ceftiofur. Conclusions and Clinical Relevance-C efepime, administered IV or IM at a dosage of 2.2 mg/kg, every 8 hours is likely to provide effective antibacterial therapy for cefepime-sen sitive organisms in horses. Further studies are needed to evaluate adv erse effects on the gastrointestinal tract.