Pharmacokinetics of azithromycin after intravenous and intramuscular administration to goats C. M. CA ´ RCELES* A. FONT* A. ESPUNY* E. FERNA ´ NDEZ-VARO ´ N* J. M. SERRANO   & E. ESCUDERO* *Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Murcia;   Department of Pharmacology, Faculty of Veterinary Medicine, University of Cordoba, Cordoba, Spain Ca ´rceles, C. M., Font, A., Espuny, A., Ferna ´ndez-Varo ´n, E., Serrano, J. M., Escudero, E. Pharmacokinetics of azithromycin after intravenous and intra- muscular administration to goats. J. vet. Pharmacol. Therap. 28, 51–55. Azithromycin is the first of a class of antimicrobial agents designated azalides. The aim of the present study was to investigate the disposition pharmacoki- netics of azithromycin in goats and determine its bioavailability. A cross-over study was carried out in two phases separated by 30 days. Azithromycin was administered at a single dose of 20 mg/kg body weight by i.v. and i.m. routes. Plasma concentrations of azithromycin were determined by a modified agar diffusion bioassay. After a single i.v. dose plasma concentrations were best fitted to a three-compartment open model. A two-compartment open model with first-order absorption fitted best after i.m. administration. The values of the pharmacokinetic parameters after i.v. administration were: half-life 32.5 h, apparent volume of distribution at the steady-state 34.5 L/kg, clearance 0.85 L/kg. and mean residence time (MRT) 40.1 h. After i.m. administration half-life of 45.2 h, a MRT of 60.3 h, maximum plasma concentration 0.64 mg/ L and a bioavalability 92.2% were obtained. The pharmacokinetic parameters of azithromycin after i.m. administration, principally its long half-life and high bioavailability, could provide an alternative to the oral route of administration in goats, although more studies are needed to establish a suitable pharmaceu- tical formulation, propose optimun dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses. (Paper received 29 April 2004; accepted for publication 4 October 2004) Dr Emilio Ferna ´ndez-Varo ´n, Department of Pharmacology, Faculty of Veterinary Medicine, University of Murcia, Campus de Espinardo, 30.071-Murcia, Spain. E-mail: emiliofv@um.es INTRODUCTION Azithomycin is the first of a class of antimicrobial agents designated azalides (Bright et al., 1988) that differ structurally from other macrolides by the insertion of a methyl-substituted nitrogen at position 9a in the lactone ring. This modification produces a significant increase in potency against Gram-negative bacteria in comparison with erythromycin with retention of the classical activity against Gram-positive bacteria (Retsema et al., 1987). Many studies have been conducted to determine the pharma- cokinetics of azithromycin in humans (Foulds et al., 1990) and some animal species (Davila & Kolacny-Babic, 1991; Hunter et al., 1995; Davis et al., 2002). Azithromycin possesses several advantages over the more commonly used macrolides. It is much more stable in an acid environment than erythromycin (Fiese & Steffen, 1990) and is well absorbed after oral administration (Girard et al., 1987) with a bioavailability that ranges from 39% in foals (Davis et al., 2002) to 97% in dogs (Shepard & Falkner, 1990). Furthermore, the distribution of azithromycin in tissues is much more extensive and the half-life in tissues and serum are much longer than the more commonly used macrolides. The objective of the present study was to determine the pharmacokinetic profile and bioavailability of azithromycin after a single-dose i.v. and i.m. administration to goats. MATERIALS AND METHODS Animals Five healthy, adult female goats weighing between 32 and 39 kg were used. The animals were housed and fed an antibiotic-free diet for at least 30 days preceding the study. Water was available ad libitum. The study was approved by the Bioethics Committee of the University of Murcia. J. vet. Pharmacol. Therap. 28, 51–55, 2005. ANTIINFECTANTS Ó 2005 Blackwell Publishing Ltd 51