title: 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.
authors.affiliation: Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
authors.forename: Mahboob
authors.initials: M
authors.lastname: Nemati
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghanbarzadeh
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006207:Half-Life; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D013608:Tablets, Enteric-Coated; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D013608:Tablets, Enteric-Coated; D014635:Valproic Acid