Effect of amphiphilic surfactant agents on the gastrointestinal absorption of albendazole in cattle

Abstract

Albendazole (ABZ) is a widely used broad-spectrum benzimidazole (BZD) anthelmintic. Low hydrosolubility and poor/erratic gastrointestinal (GI) absorption play against the systemic availability and resultant clinical efficacy of BZD compounds. Different strategies are currently investigated to improve their bioavailability and efficacy in different animal species and humans. Surfactant agents facilitate dissolution of lipophilic drugs and increase membrane permeability. The influence of amphiphilic surfactants on the pattern of absorption and systemic availability of ABZ and its metabolites in cattle was characterized in the current trial. Twenty (20) parasite-free Holstein calves (100-120 kg) were randomly allocated into four groups and treated intraruminally (10 mg/kg) using one of the following ABZ suspensions: control without surfactant (75/25 dimetyl sulphoxide/saline solution) (group A), 5 mM sodium taurocholate (STC) in saline solution (group B), 8.27 mM sodium lauryl sulphate (SLS) in saline solution (group C) and a commercial formulation (Valbazen((R)), Pfizer Inc. SA) (group D). Jugular blood samples were taken over 72 h post-treatment and plasma analysed by HPLC. Albendazole sulphoxide (ABZSO) and sulphone were the metabolites found in plasma. STC did not affect ABZ absorption while increased ABZSO peak plasma concentration (C(max)) (158% higher, P<0.001) was observed following co-administration of ABZ plus SLS, compared to the control group without surfactant. ABZSO plasma availability was significantly greater after the ABZ-SLS (164%) co-administration compared to that obtained in the control group without surfactant. A similar ABZSO plasma availability was obtained following the treatments with the ABZ-SLS and the commercially available formulation. SLS-mediated enhanced dissolution and absorption of ABZ accounted for the observed increased systemic availability of the active ABZSO metabolite in cattle. These results should be considered among strategies to improve the use of BZD anthelmintics.

Comparative assessment of the access of albendazole, fenbendazole and triclabendazole toFasciola hepatica: effect of bile in the incubation medium

“…This increases the surface area enormously and facilitates the diffusion across the lipid membrane into the cell. Solubilization into simple bile salt micelles has been reported for many poorly water-soluble drugs, which has been correlated with higher intestinal drug absorption (Del Estal et al 1993 ;Virkel et al 2003). Drug solutions in micellar media consist of 2 separate phases : an aqueous phase with a fraction of the drug free in solution, and a micellar phase with the remaining fraction of the drug solubilized in micelles (Poelma et al 1991).…”

Strategies to Optimize the Efficacy of Anthelmintic Drugs in Ruminants

“…Different pharmacotechnical strategies have been assayed to overcome their lack of water solubility (Table I). Amphiphilic surfactants improved the absorption and systemic availability of albendazole metabolites in cattle [102]. Complexation with cyclodextrins markedly increased the plasma availability of flubendazole metabolites in mice and pigs [103,104] compared to a conventional suspension.…”

Medical Treatment for Neurocysticercosis: Drugs, Indications and Perspectives

“…Studies in cattle have shown that sodium taurocholate increases ABZSO Cmax levels in 150% while sodium lauryl sulfate increases bioavailability in 164% [51]. Studies in cattle have shown that sodium taurocholate increases ABZSO Cmax levels in 150% while sodium lauryl sulfate increases bioavailability in 164% [51].…”