Fasted state bioavailability of two delayed release formulations of divalproex sodium in healthy Iranian volunteers.

Abstract

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.