title: Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep.
abstract: Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. 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 80mg/kg. After a transient aparasitaemic period, all animals 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 understand 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 8h 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. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route.
authors.affiliation: Institut d'Epidémiologie Neurologique et de Neurologie Tropicale (EA3174), Faculté de Médecine, 2 rue du Docteur Marcland, 87025 Limoges Cedex, France. caroboda@yahoo.fr
authors.forename: Caroline
authors.initials: C
authors.lastname: Boda
authors.forename: Bertin
authors.initials: B
authors.lastname: Enanga
authors.forename: Hélène
authors.initials: H
authors.lastname: Dumet
authors.forename: Gérard
authors.initials: G
authors.lastname: Chauviere
authors.forename: François
authors.initials: F
authors.lastname: Labrousse
authors.forename: Claude
authors.initials: C
authors.lastname: Couquet
authors.forename: Sylvie
authors.initials: S
authors.lastname: Saivin
authors.forename: Georges
authors.initials: G
authors.lastname: Houin
authors.forename: Jacques
authors.initials: J
authors.lastname: Perie
authors.forename: Michel
authors.initials: M
authors.lastname: Dumas
authors.forename: Bernard
authors.initials: B
authors.lastname: Bouteille
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001831:Body Temperature; D001835:Body Weight; D002555:Cerebrospinal Fluid / Q000737:chemistry; D005260:Female; D006207:Half-Life; D008892:Milk / Q000737:chemistry; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood* / Q000188:drug therapy / Q000469:parasitology; D013830:Thiadiazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014346:Trypanosoma brucei brucei / Q000254:growth & development*; D014353:Trypanosomiasis, African / Q000097:blood* / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*
chemical_list: D000981:Antiprotozoal Agents; D013830:Thiadiazoles; C013378:megazol