Research in Veterinary Science /990. 49, 34-38 Pharmacokinetic profile of cefotaxime in goats M. ATEF, A. RAMADAN, N. A. AFIFI, S. A. H. YOUSSEF, Department of Pharmacology, Cairo University, Giza, Egypt Cefotaxime was administered to goats intravenously, intramuscularly and subcutaneously to determine blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injec- tion, the blood concentration-time curve indicated a two compartment open model, with an elimination half-life value (tvzl3) of 22·38 ± 0·41 minutes. Both intramuscular and subcutaneous routes showed slower values, that is, 38·64 and 69·58 minutes. The apparent volume of distribution of cefotaxime in goats was less than 1 litre kg -I and suggested a lower distribution in tissues than in blood. After intra- muscular and subcutaneous injections peak plasma cefotaxime concentrations were 77·8 ± 1· 7 and 44·0 ± 0·8 ",g ml- I at 29·6 and 40·4 minutes, respec- tively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1·08 and 1·25 times the intravenous availability, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration. CEFOTAXIME, a third generation cephalosporin, is more active against Gram-negative organisms than earlier cephalosporins particularly penicillin induced (3-lactamaseproducing bacteria. In vitro studies with cefotaxime indicate that a concentration of 1",g ml- I of microbiological media culture broth would inhibit the growth of most strains of Haemophilus, Proteus, Citrobacter, Salmonella, Escherichia and Klebsiella species, but Enterobacter and Serratia species are slightly moreresistant, requiring a concentration of 2 to 4 ",g ml- I to inhibit most strains. Also 8 ",g ml- I will inhibit half the strains of bacteroides (Hamilton- Miller et al1978, Schriner et aI1980). The appropriate use of cefotaxime in small animals is limited by a lack of pharmacological data. Cefotaxime has been recommended for treatment of bacterial diseases because of its relatively wide spectrum of activity, greater resistance to lactamases than previously used (3-lactam antibiotics (Kalager et al 1982) and a wide safety margin in relation to renal toxicity (Regamey 1985). Cefotaxime is at present available for use in human beings, but it is not approved for use in animals in the USA. Elsewhere, the use of cephalo- sporins in veterinary practice has been restricted by a lack of pharmacokinetic data in each of the major species of domesticated animals (Powers and Garg 1980).The disposition of the drug in blood plasma of ruminants has not been analysed by the technique of pharmacokinetic modelling. As the intramuscular injection of many antimicrobial drugs in small animals isoften more painful than their subcutaneous administration (English 1983), it could be advan- tageous to administer cefotaxime subcutaneously, with the possibility of prolonged plasma drug con- centration (Guerrini et aI1983). The present study was therefore initiated to describe the pharmacokinetic profile of cefotaxime in goats and to explore its kinetic disposition after intramuscular and sub- cutaneous administration. Materials and methods Animals Five clinically healthy one- to two-year-old goats (belonging to the Faculty of Veterinary Medicine, Cairo University) weighing from 12 to 17 kg (average bodyweight 15'0 ± 0'84 kg SE) were obtained four weeks before the study began. During the acclimatisa- tion and subsequent treament periods, they were fed alfalfa, and drinking water was freely available. The animals were kept in individual metabolic cages in an enclosed room. They were sheared over a jugular vein to facilitate collection of blood samples. Drug administration Each animal was given 50 mg kg- I body weight doses of a 25 per cent weight/volume aqueous solution of cefotaxime sodium (Claforan; Hoechst). The drug was administered to each animal by rapid intravenous, deep intramuscular (gluteal muscle), or subcutaneous (prescapular region) injection, in three separate experiments at intervals of one week. All five goats were injected by the same route on each dosing day. 34