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Abstract

The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

“…Regarding ABZSO 2 , as mentioned above, its concentration-time pattern is also similar to those obtained in previous studies [ 11 , 21 , 25 , 41 , 42 , 43 ]. In our study, ABZSO 2 pharmacokinetic parameters show no significant variation in either the amount or the rate of incorporation of this metabolite into the blood.…”

“…The rate of dissolution in the gastrointestinal tract of benzimidazoles is thought to be critical in achieving adequate absorption and, consequently, clinical efficacy. Different approaches have been assessed to increase its oral bioavailability, including alternative drug formulations to improve aqueous solubility [ 2 , 21 ], interferences in liver biotransformation [ 15 , 22 ], and non-chemical strategies, such as management of feed intake [ 23 , 24 ] or prior fasting to administration [ 25 , 26 ]. Although these approaches have improved the knowledge on the pharmacokinetic behavior of ABZ, none of them has been finally translated into the SPC of the medicinal products containing ABZ and thus, to daily clinical practice.…”

Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers

“…Changes in the GI absorption of ALB modulated by diet have been demonstrated in different animal species (22)(23)(24)(25). In ruminants, starvation decreases the flow rate of the digesta through the GI tract, improving drug dissolution, absorption, and exposure of benzimidazole compounds (9,24,26).…”

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

“…Different physio-pharmacology based strategies have been assayed to increase BZD drug availability and their resultant pharmacological activity in ruminant species. Approaches such as management of feed intake (Ali and Hennessy, 1995), fasting the animals prior to treatment (Lifschitz et al, 1997;Sanchez et al, 2000), and interference with the pattern of liver biotransformation (Benchaoui and Mckellar, 1996;Lanusse et al, 1993b;Sanchez et al, 1996;Sanchez et al, 2002), have been shown to increase the systemic availability and/or residence time of active BZD molecules in the animal host.…”