Veterinary Parasitology 121 (2004) 213–223 Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep Caroline Boda a,∗ , Bertin Enanga a , Hélène Dumet b , Gérard Chauviere c , François Labrousse d , Claude Couquet b , Sylvie Saivin e , Georges Houin e , Jacques Perie c , Michel Dumas a , Bernard Bouteille a a Institut d’Epidémiologie Neurologique et de Neurologie Tropicale (EA3174), Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France b Laboratoire Départemental d’Analyses et Recherches Vétérinaires de la Haute-Vienne, av Prof Joseph de Léobardy 87000 Limoges Cedex, France c Groupe de Chimie Organique Biologique UMR-CNRS 5068, Université Paul Sabatier, 118 Route de Narbonne, B ˆ at. IIR1-B2, 31062 Toulouse Cedex 4, France d Laboratoire d’anatomie pathologique, CHU Dupuytren, 2 av Martin Luther King 87042 Limoges Cedex, France e Laboratoire de Pharmacocinétique et Toxicologie Clinique, CHU Rangueil-Larrey, 1 av Prof Jean Poulhes 31403 Toulouse Cedex, France Received 21 August 2003; received in revised form 30 January 2004; accepted 9 February 2004 Abstract Experimentally infected sheep have been previously developed as an animal model of try- panosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80 mg/kg. After a transient aparasitaemic period, all an- imals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to under- stand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8 h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. ∗ Corresponding author. Tel.: +33-5-55-43-58-20; fax: +33-5-55-43-58-21. E-mail address: caroboda@yahoo.fr (C. Boda). 0304-4017/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.vetpar.2004.02.027