title: 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.
authors.affiliation: Laboratorio de Farmacología, Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, UNCPBA, (7000) Tandil, Buenos Aires, Argentina. gvirkel@vet.unicen.edu.ar
authors.forename: Guillermo
authors.initials: G
authors.lastname: Virkel
authors.forename: Fernanda
authors.initials: F
authors.lastname: Imperiale
authors.forename: Adrián
authors.initials: A
authors.lastname: Lifschitz
authors.forename: Alejandra
authors.initials: A
authors.lastname: Pis
authors.forename: Ana
authors.initials: A
authors.lastname: Alvarez
authors.forename: Gracia
authors.initials: G
authors.lastname: Merino
authors.forename: Julio
authors.initials: J
authors.lastname: Prieto
authors.forename: Carlos
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D015766:Albendazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D013501:Surface-Active Agents / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D013501:Surface-Active Agents; D015766:Albendazole