ALVAREZ Luis Ignacio
Pharmacokinetic comparison of different flubendazole formulations in pigs: A further contribution to its development as a macrofilaricide molecule
L. CEBALLOS A, *, L. ALVAREZ A, C. MACKENZIE B, T. GEARY C, C. LANUSSE A
INTERNATIONAL JOURNAL FOR PARASITOLOGY: DRUG AND DRUG RESISTANCE
ELSEVIER SCIENCE BV
Año: 2015 vol. 5 p. 178 - 184
Despite the well established ivermectin activity against microfilaria, the success of human filariasiscontrol programmes requires the use of a macrofilaricide compound. Different in vivo trials suggest thatflubendazole (FLBZ), an anthelmintic benzimidazole compound, is a highly efficacious and potentmacrofilaricide. However, since serious injection site reactions were reported in humans after the subcutaneousFLBZ administration, the search for alternative pharmaceutical strategies to improve thesystemic availability of FLBZ has acquired special relevance both in human and veterinary medicine. Thegoal of the current experimental work was to compare the pharmacokinetic plasma behavior of FLBZ,and its metabolites, formulated as either an aqueous hydroxypropyl- b -cyclodextrin-solution (HPBCD),an aqueous carboxymethyl cellulose-suspension (CMC) or a Tween 80-based formulation, in pigs. Animalswere allocated into three groups and treated (2 mg/kg) with FLBZ formulated as either a HPBCDsolution(oral), CMC-suspension (oral) or Tween 80-based formulation (subcutaneous). Only traceamounts of FLBZ parent drug and its reduced metabolite were measured after administration of thedifferent FLBZ formulations in pigs. The hydrolyzed FLBZ (H-FLBZ) metabolite was the main analyterecovered in the bloodstream in pigs treated with the three experimental FLBZ formulations. The oraladministration of the HPBCD-solution accounted for significantly higher (P < 0.05) Cmax and AUC(23.1 ± 4.4 mg h/mL) values for the main metabolite (H-FLBZ), compared with those observed for the oralCMC-suspension (AUC ¼ 3.5 ± 1.0 mg h/mL) and injectable Tween 80-based formulation (AUC:7.5 ± 1.7 mg h/mL). The oral administration of the HPBCD-solution significantly improved the poor absorptionpattern (indirectly assessed as the H-FLBZ plasma concentrations) observed after the oraladministration of the FLBZ-CMC suspension or the subcutaneous injection of the Tween 80 FLBZformulation to pigs. Overall, the work reported here indicates that FLBZ pharmacokinetic behavior can bemarkedly changed by the pharmaceutical formulation.