Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

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 (ABZSO2, 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 ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) 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 Cmax (tmax) (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 ABZSO2, Cmax, AUC and tmax 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.

Photoredox and Vanadate Cocatalyzed Hydrolysis of Aryl Ethers at Ambient Temperature

“…The aryl methyl ether containing an easily hydrolyzed ester group and decarboxylated β-ketoester structural unit ( 1by ) afforded the corresponding phenol in 55% yield . Furthermore, a methyl ester of the choleretic drug menbutone ( 1bz ) as a derivative of 1-methoxynaphthalene resulted in a moderated yield of 40%. It is evident that the hydrolysis of aryl ethers developed in this study offers a unique transformation in organic transformations and pharmaceutical intermediate modification.…”

Pharmacokinetics of menbutone after intravenous and intramuscular administration to sheep

“…The choleretic properties of menbutone, increasing bile secretion to intestine, may be used to favor the absorption of compounds with poor water solubility. For instance, it has been shown that this drug has significantly augmented the absorption of the anthelmintic metabolite albendazole sulphoxide from the intestinal lumen in sheep ( 16 ). Menbutone would act in a similar way as a fatty meal in healthy human subjects.…”