Comparative drug systemic exposure and clinical efficacy against resistant nematodes in lambs treated with different albendazole formulations G. SUA ´ REZ* L. ALVAREZ  , à D. CASTELLS § O. CORREA – P. FAGIOLINO** & C. LANUSSE  , à *Laboratorio de Farmacologı ´a, Facultad de Veterinaria, Universidad de la Repu ´blica (UDELAR), Montevideo, Uruguay;   Laboratorio de Farmacologı ´a, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil, Argentina; à Consejo Nacional de Investigaciones Cientı ´ficas y Te ´cnicas (CONICET), Argentina; § Secretariado Uruguayo de la Lana (SUL), Florida, Uruguay; – Laboratorio de Parasitologı ´a, Facultad de Veterinaria, Universidad de la Repu ´blica (UDELAR), Montevideo, Uruguay; **Departamento de Ciencias Farmace ´uticas, Facultad de Quı ´mica, Universidad de la Repu ´blica (UDELAR), Montevideo, Uruguay Sua ´rez, G., Alvarez, L., Castells, D., Correa, O., Fagiolino, P., Lanusse, C. Comparative drug systemic exposure and clinical efficacy against resistant nematodes in lambs treated with different albendazole formulations. J. vet. Pharmacol. Therap. 34, 557–564. A pharmaco-parasitological assessment of four different albendazole (ABZ) formulations was carried out in lambs infected with multiple resistant gastrointestinal (GI) nematodes. The comparative drug systemic exposure profiles (ABZ sulphoxide plasma concentrations) and anthelmintic efficacies (clinical endpoint measured through the faecal nematode eggs reduction counts) were determined for a reference formulation (RF) and three different test (T1, T2, T3) generic ABZ preparations. Fifty (50) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into five experimental groups (n = 10). Animals in each group received treatment with either the RF, one of the test ABZ formulations (5 mg ⁄ kg by the intraruminal route) or were kept as untreated control. Blood samples were collected over 48 h post-treatment. ABZ parent drug was not recovered in the bloodstream. The ABZ sulphoxide (ABZSO) and sulphone (ABZSO 2 ) metabolites were measured in plasma by ultraviolet high-performance liquid chromatography over 36–48 h post-treatment. A faecal nematode egg count reduction test (FECRT) was performed at day 10th post-treatment to lambs from all treated and untreated groups, which indicated the predominance of nematodes with high level of resistance to ABZ. Both ABZSO C max and AUC 0–LOQ values obtained for the RF (pioneer product) were significantly higher (P< 0.05) than those obtained for the T1 and T3 preparations. Based on the currently available bioequivalence criteria, the test (generic) ABZ formulations under evaluation could not be considered equivalent to the RF regarding the rate (C max ) and extent (AUC 0–LOD ) of drug absorption (indirectly estimated through the ABZSO metabolite). A large variation in nematode egg counts did not permit to obtain statistically significant differences among formulations. However, a favourable trend in the efficacy against the most resistant nematodes was observed for the formulations with the highest ABZSO systemic exposure. (Paper received 25 September 2010; accepted for publication 16 December 2010) Prof. Carlos Lanusse, Laboratorio de Farmacologı ´a, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario (7000), Tandil, Argentina. E-mail: clanusse@vet.unicen.edu.ar INTRODUCTION Albendazole (ABZ) is a broad-spectrum benzimidazole anthel- mintic drug widely used in veterinary medicine (McKellar & Scott, 1990; McKellar & Jackson, 2004). Albendazole sulphoxide (ABZSO) and sulphone (ABZSO 2 ) are the main metabolites recovered in the bloodstream after ABZ administration to sheep (Marriner et al., 1985). ABZ metabolites concentration profiles measured in the bloodstream correlate with those recovered from mucosa and fluids from different gastrointestinal (GI) sections (Alvarez et al., 1999, 2000). The plasma ⁄ GI tract distribution of the active sulphoxide metabolites is of major relevance for the efficacy of benzimidazole anthelmintics against GI parasites (Lanusse & Prichard, 1993). Several oral ⁄ intraruminal ABZ formulations for use in sheep are worldwide available in the pharmaceutical veterinary J. vet. Pharmacol. Therap. 34, 557–564. doi: 10.1111/j.1365-2885.2011.01274.x. Ó 2011 Blackwell Publishing Ltd 557