Comparative drug systemic exposure and clinical efficacy against resistant nematodes in lambs treated with different albendazole formulations

Authors

  • G. SUÁREZ,

    1. Laboratorio de Farmacología, Facultad de Veterinaria, Universidad de la República (UDELAR), Montevideo, Uruguay
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  • L. ALVAREZ,

    1. Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil, Argentina
    2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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  • D. CASTELLS,

    1. Secretariado Uruguayo de la Lana (SUL), Florida, Uruguay
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  • O. CORREA,

    1. Laboratorio de Parasitología, Facultad de Veterinaria, Universidad de la República (UDELAR), Montevideo, Uruguay
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  • P. FAGIOLINO,

    1. Departamento de Ciencias Farmacéuticas, Facultad de Química, Universidad de la República (UDELAR), Montevideo, Uruguay
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  • C. LANUSSE

    1. Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires (UNCPBA), Campus Universitario, Tandil, Argentina
    2. Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina
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Prof. Carlos Lanusse, Laboratorio de Farmacología, Facultad de Ciencias Veterinarias, UNCPBA, Campus Universitario (7000), Tandil, Argentina. E-mail:clanusse@vet.unicen.edu.ar

Abstract

Suárez, 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 (ABZSO2) 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 Cmax and AUC0–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 (Cmax) and extent (AUC0–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.

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