Fasted state bioavailability of two delayed release formulations of divalproex sodium in healthy Iranian volunteers.
Author(s): Zakeri-Milani P, Nemati M, Ghanbarzadeh S, Hamishehkar H, Valizadeh H
Affiliation(s): Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Publication date & source: 2011, Arzneimittelforschung., 61(8):439-43.
Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
The purpose of this study was to compare the pharmacokinetics and bioavailability of two commercial brands of delayed release divalproex sodium (CAS 76584-70-8) tablets in healthy male Iranian volunteers in fasted state. Each single-dose, randomized, open-label, blind study was conducted according to a crossover design in subjects. A washout interval of 14 days separated the doses in each study. Serial venous blood samples were obtained over 24 h after each administration to measure drug in serum, and placed into tubes containing sodium heparin. Then the separated plasma was kept frozen at -20 degrees C for subsequent analysis. The plasma concentrations of drug were analyzed by a validated sensitive HPLC method with UV detection. Mean maximum serum concentrations of 124.5 +/- 34.8 microg/ml and 134.2 +/- 31.1 microg/ml were obtained for the test and reference products, respectively. The AULo(t) and AUCo(infinity) were 2023.8 +/- 578.8 1 microg h/ml and 2705.3 +/- 792.1 microg h/ml for the test and 2068.2 +/- 526.4 microg h/ml and 2729.6 +/- 698.2 microg h/ml for the reference formulation, respectively. The calculated 90% confidence intervals for the ratio of C(max) (87.2-101.5%), AUCo(t) (92.1-108.6%) and AUCo(infinity) (93.1-110.6%) values for the test and reference products were all within the 85-120% interval proposed by the FDA and EMA. Therefore the divalproex sodium tablets of the test and reference products are bioequivalent in terms of rate and extent of absorption.