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 °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 μg/ml and 134.2 ± 31.1 μg/ml were obtained for the test and reference
products, respectively. The and were 2023.8 ± 578.8 1 μg h/ml and 2705.3 ± 792.1 μg
h/ml for the test and 2068.2 ± 526.4 μg h/ml and 2729.6 ± 698.2 μg h/ml for the reference
formulation, respectively. The calculated 90% confidence intervals for the ratio of
Cmax (87.2-101.5%), (92.1-108.6%) and (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.
Key words
Bioavailability - Delayed release tablets - Divalproex sodium - Fasted state
