Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats.

Dilek Aksit,Selim Sekkin,Cengiz Gokbulut,Hande Sultan Yalinkilinc,Veli Yilgor Cirak,Murat Boyacioğlu,Erol Ayaz

doi:10.1186/s12917-015-0442-5

Abstract

BackgroundThe aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 mg/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. A total of 16 goats (Capra aegagrus hircus, eight males and eight females) and 8 sheep (Ovis aries, four males and four females) 12–16 months old and weighing 20–32 kg, were used. The study was designed according to two-phase crossover study protocol. In Phase-1, eight sheep were assigned as Group I and 16 goats were allocated into two groups (Group II and Group III). ABZ-SO was applied to Group I (sheep) and Group II (goats) animals subcutaneously, and to Group III (goats) animals intravenously, all at a dose rate of 5 mg/kg BW. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. Blood samples were collected from the jugular vein at different times between 1 and 120 h after drug administrations. The plasma concentrations of ABZ-SO and its metabolites were analysed by high performance liquid chromatography.ResultsIn goats, the area under the curve, terminal half-life and plasma persistence of ABZ-SO were significantly smaller and shorter, respectively, compared with those observed in sheep following both IV and SC administrations at a dose of 5 mg/kg BW. On the other side, dose-dependent plasma dispositions of ABZ-SO were observed following SC administration at increased doses (10 and 15 mg/kg) in goats.ConclusionsConsequently, ABZ-SO might be used at higher doses to provide higher plasma concentration and thus to achieve greater efficacy against the target parasites.

Highlights

The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 mg/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration
The plasma concentration vs. time curves of ABZ-SO and Albendazole sulfone (ABZ-SO2) are shown in Fig. 1 and the pharmacokinetic data are summarized in Table 2 following IV administration in goats and sheep
The absorption phase and peak plasma concentrations (Cmax) of ABZ-SO were similar in both species, the area under the curve (AUC), terminal half-life (T1/2) and plasma persistence (MRT) values were smaller and shorter, respectively, in goats compared with those observed in sheep after SC administration at a dose of 5 mg/kg BW

Summary

Introduction

The aims of this study were to compare the pharmacokinetics of albendazole sulfoxide (ABZ-SO, ricobendazole) in goats and sheep at a dose of 5 mg/kg bodyweight (BW), after intravenous (IV) and subcutaneous (SC) administrations, and to investigate the effects of increased doses (10 and 15 mg/kg BW) on the plasma disposition of ABZ-SO in goats following SC administration. In Phase-2, the sheep in the Group I received ABZ-SO intravenously in a dose of 5 mg/kg BW; the goats in Group II and Group III received ABZ-SO subcutaneously at a dose of 10 mg/kg and 15 mg/kg BW, respectively. An injectable formulation of ABZ-SO has been developed for subcutaneous (SC) administration in cattle and sheep This formulation has some advantages compared with the other formulations for per os or intraruminal administration, as drug molecules are potentially freely available for absorption from the injection site, avoiding the first-pass effect and actions of the oesophageal groove [8]. The gastrointestinal and the first-pass metabolism are common metabolic pathways for sulfoxide BZDs and they are metabolised into their sulfoxides, which in turn are oxidized into the more polar and less anthelmintically active sulfone metabolites following per os administration in different animal species

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