Ex vivo diffusion of albendazole and its sulfoxide metabolite into Ascarissuum and Fasciola hepatica

The current experiments compare the pattern of ex vivo uptake (diffusion) o f albendazole (ABZ) and albendazole sulfoxide (ABZSO) by Ascaris suum and F asciola hepatica. Specimens of A. suum and F. hepatica were collected from untreated animals (pigs and sheep, respectively) and incubated with either ABZ or ABZSO for different time periods (5-180 min). After incubation, the parasite material was analysed by HPLC to quantify the amount of ABZ and/or ABZSO. The parent drug and its active ABZSO metabolite were recovered from the parasites after ex vivo incubation for different time periods througho ut the assay. Total drug availability in A. suum., expressed as area under the concentration versus time curve (AUC) over 180 min of incubation, was s ignificantly greater (P < 0.05) for ABZ parent drug (AUC = 4.19 +/- 0.59 mu g.h.g(-1)) compared with the more polar ABZSO metabolite (AUC = 0.25 +/- 0. 01 mug.h.g(-1)). Similar results were observed after the incubation of both molecules with F. hepatica. where the AUC values obtained were 10.6 +/- 0. 28 mug.h.g(-1) and 2.04 +/- 0.33 mug.h.g(-1) for ABZ and ABZSO, respectivel y. The greater diffusion and availability of ABZ in both helminths correlat e with the higher lipophilicity or the parent drug, compared with its sulfo xide metabolite. The amount of both molecules measured in A. suum was signi ficantly lower (P < 0.05) than that recovered in F. hepatica. The complexit y of the histological structure of the nematode cuticle compared with the e xternal tegument of the trematode may account for such a difference in drug diffusion between the species. These findings complement previous observat ions on the patterns of in vivo uptake of ABZ by different helminth parasit es, contributing to the understanding of the pharmacological anthelmintic a ction of these moieties.