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Absolute Bioavailability and Absorption Characteristics of Divalproex Sodium Extended‐Release Tablets in Healthy Volunteers
Author(s) -
Dutta Sandeep,
Reed Ronald C.,
Cavanaugh John H.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004266782
Subject(s) - divalproex , bioavailability , valproic acid , chemistry , absorption (acoustics) , pharmacology , pharmacokinetics , area under the curve , medicine , materials science , bipolar disorder , mania , composite material , psychiatry , lithium (medication) , epilepsy
Conventional delayed‐release, enteric‐coated divalproex sodium tablet has an absolute bioavailability of ∼100%. Divalproex sodium extended‐release (ER) tablet is a novel formulation of valproic acid (VPA) designed to release the drug slowly at a constant zero‐order rate. The purpose of this study was to evaluate the absolute bioavailability and absorption characteristics of divalproex ER. Healthy adult volunteers (n = 16) received divalproex ER and intravenous VPA in crossover fashion. Absolute bioavailability was calculated as the divalproex ER/intravenous VPA ratio of area under the curve extrapolated to infinity. The duration and rate of absorption of VPA from divalproex ER tablets were determined by deconvolution analysis. The geometric mean absolute bioavailability of divalproex ER was 0.896. The mean (coefficient of variation) duration of drug absorption from divalproex ER was 21.8 (17%) hours, and the zero‐order absorption rate was 21.6 (24%) mg/h for a 500‐mg tablet. Divalproex ER has a lower absolute bioavailability than conventional divalproex tablets but exhibits good extended‐release characteristics without any dose dumping