Comparative hepatic metabolism of the anthelmintic flubendazole in rat, swine and sheep

VIRKEL G.; MATÉ L.; LIFSCHITZ A.; CEBALLOS L.; ALVAREZ L.; LANUSSE C.

Amsterdam

Congreso; 12th International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2012

Organizing Committee of the 12th International Congress of the European Association for Veterinary Pharmacology and Toxicology

INTRODUCTION Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic widely used in pigs and poultry. This drug has shown good efficacy to control gastrointestinal nematodes in sheep and macrofilaria in lymphatic filariasis and onchocerciasis in man (Mackenzie & Geary, 2011). Flubendazole contains a ketone group at position -5 of the benzimidazole ring which has implications on its metabolic pattern. For instance, carbonyl-reducing enzymes catalyze the NADPH-dependent conversion of FLBZ into its reduced metabolite (red-FLBZ) in sheep liver (Maté et al., 2008; Bártíková et al., 2010).The aim of the current work was to assess the comparative FLBZ metabolism pattern in rat, swine and sheep liver cytosolic and microsomal fractions. MATERIALS AND METHODS Liver microsomal and cytosolic fractions were obtained from male (n=3) and female (n=3) Wistar rats, male Texel lambs (n=6) and male Landrace piglets (n=4). Flubendazole keto-reduction was assessed by the rate of red-FLBZ formation in the presence of NADPH. Incubations with red-FLBZ as substrate were also carried out in the presence of NADP+. Substrates were incubated at 100 µM (15 min at 37ºC) and samples were analyzed by HPLC. Statistical comparisons among species were performed using non-parametric ANOVA. RESULTS Both liver cytosolic and microsomal fractions from each animal species were able to metabolize FLBZ into red-FLBZ. The cytosolic production of the red-FLBZ was higher (p