Dose dependent pharmacokinetics of albendazole in human

Abstract

Pharmacokinetics of albendazole sulphoxide (ABZ‐SO) in three different single oral doses of albendazole (ABZ) (400, 800 and 1200 mg) was studied in 10 healthy human volunteers in a double blind three‐way crossover design. The serum levels of albendazole main metabolite, albendazole sulphoxide (ABZ‐SO), were analysed by a modified high‐pressure liquid chromatography method. (ABZ is not detectable in biological fluids itself.) For ABZ‐SO, there was no significant difference in the biological half life, normalized serum peak concentration (C_{max−ABZ−SO}/Dose_ABZ), time to reach peak concentration (T_max) and mean residence time (MRT), whereas apparent clearance (Cl_p/F), apparent distribution volume (V_d/F), normalized area under the serum concentration‐time curve (AUC_ABZ−SO/Dose_ABZ) and normalized area under the first moment curve (AUMC_ABZ−SO/Dose_ABZ) of albendazole main metabolite (ABZ‐SO) were statistically different at different doses of the parent drug, resulting in substantially lower serum concentration and thereafter AUC_ABZ−SO/Dose_ABZ and AUMC_ABZ−SO/Dose_ABZ in higher doses. These observations indicate dose dependent pharmacokinetics of albendazole (observed for ABZ‐SO), which were explained on the basis of a change in fraction of dose absorbed (F) as a result of slow and incomplete dissolution of the main drug in the GI tract. Copyright © 2002 John Wiley & Sons, Ltd.