Modification of albendazole pharmacokinetics by menbutone administration in calves

Abstract

Optimizing the use of the existing anthelmintics has become a priority, as resistance is a growing concern worldwide and the development of novel antiparasitic drugs slow. The paper describes the pharmacokinetic interaction between the antiparasitic albendazole (ABZ) and the choleretic drug menbutone (MEN) in calves, when ABZ was administered orally (7.5 mg/kg) alone or with intramuscular MEN (10 mg/kg) (1 or 2 doses 24 h apart) to 12 animals. Blood samples were collected at 14 sampling points over 72 h, and plasma concentrations of ABZ, albendazole sulfoxide (ABZSO, active metabolite), and albendazole sulfone (ABZSO2, inactive one) were measured using high performance liquid chromatography (HPLC). Pharmacokinetic parameters were calculated with non-compartmental methods. No ABZ was detected at any sampling time, whereas ABZSO was determined for longer than ABZSO2. A significant increase in systemic exposure of ABZSO was observed following concomitant administration of MEN, with a mean ABZSO maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) 33.5 and 31.8% higher, respectively, when a dose of MEN was administered. The second administration of MEN did not improve the amount absorbed compared with a single dose of the choleretic drug. As for ABZSO2, Cmax, AUC and tmax values were similar regardless the treatment followed (ABZ alone or with one or two doses of MEN). Thus, our results show that the simultaneous administration of ABZ with a single dose of MEN in cattle may increase the amount of ABZSO and maintain the efficacy of ABZ, whereas a second dose of MEN offers no such benefit.