Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

SIMPLE SUMMARY: Anthelmintic drugs are among those most widely used in veterinary practice. The development of resistance to these drugs is a widespread problem, especially in small ruminants, and represents a serious threat to animal production. Thus, new possibilities to use the available pharmacological groups in a more efficient way should be explored. The objective of this study was to assess the pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) in sheep, and it may result in greater effectivity of this drug against nematode parasites. Plasma concentrations of ABZSO (ABZ active metabolite) were higher when ABZ was administered with MEN. The proposed interaction is a simple, safe, and inexpensive way of increasing the effectivity of this anthelmintic widely used in livestock. ABSTRACT: The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO(2), inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO(2) from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach C(max) (t(max)) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO(2), C(max), AUC and t(max) values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.