Dose dependent pharmacokinetics of albendazole in human.
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.
Mirfazaelian
A
A
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155/6451, Tehran, Iran.
Rouini
M R
MR
Dadashzadeh
S
S
D000328:Adult; D015766:Albendazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male
D000871:Anthelmintics; D015766:Albendazole