The binding and distribution of albendazole and its principal metabolites in Giardia duodenalis

Trophozoites of the protozoan parasite Giardia duodenalis were exposed to v arious albendazole concentrations for 4 h, washed, fixed and incubated with antibodies raised against albendazole and its two major metabolites albend azole sulphoxide and albendazole sulphone. Tubulin antibodies were also use d. A peroxidase- or FITC-conjugated secondary antibody was used to detect t he primary antibody with transmission electron microscopy or confocal laser scanning microscopy, respectively. Albendazole, a benzimidazole compound, was detected in the mid-dorsal region of trophozoites, albendazole sulphoxi de in the posterior-dorsal region and albendazole sulphone in clusters abov e the median bodies. Tubulin was recognised in the ventral disk. This is th e first indication that C. duodenalis may be capable of metabolising albend azole and the potential path of the metabolised drug traced within the trop hozoite. Fluorescence measurements revealed that albendazole sulphoxide bin ding decreased and albendazole sulphone binding increased with exposure of the trophozoites to increasing albendazole concentration. This indicates th at if albendazole was being metabolised by trophozoites, it occurred to a g reater extent following exposure to higher albendazole concentrations.