Abstract
Simple SummaryAnthelmintic 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.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.
Highlights
albendazole sulphoxide (ABZSO) mean concentrations were always higher than those detected for ABSZO2 until 30 h, falling below those values determined for the inactive metabolite from this sampling time onwards
Pharmacokinetic parameters obtained in our study are compared only with those indicated by other authors after ABZ administration by the oral route to sheep at the same dose (5 mg/kg), as a lack of proportionality was described for some ABZSO parameters (Cmax and area under the plasma concentration-time curve (AUC)), with increasing dosage in this animal species [45]
The results obtained here show that MEN, when administered with ABZ, was able to increase plasma concentrations of ABZSO and, its anthelmintic effect, but we have evaluated the interaction between ABZ and MEN with the lowest dose (5 mg/kg)
Summary
Its low aqueous solubility is a major disadvantage, since ABZ is poorly absorbed after oral administration, which limits its clinical use [1,2]. ABZ plasma disposition has been widely studied in different animal species, including ruminants [5,6,7,8,9,10,11,12,13,14,15]. In these latter animal species, the drug undergoes a complex and extensive biotransformation. The rumen acts as a drug reservoir, being released slowly into the abomasum, where the acidic pH improves its dissolution
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