Comparison of the bioavailability of 250 and 500 mg divalproex sodium extended-release tablets in healthy volunteers.

Abstract

Divalproex sodium extended-release tablet (divalproex-ER), 500 mg strength, is approved for use in the prophylaxis of migraine headaches and epilepsy. The bioavailability of novel 250 mg divalproex-ER formulations, under development to allow greater flexibility in dosing, was compared with the available 500 mg divalproex-ER in a single-dose, fasting and nonfasting, randomized, open-label, crossover study in healthy adult volunteers. One group of 15 subjects was dosed after a 10 h overnight fast and another group of 24 subjects was dosed after a high-fat breakfast. Plasma valproic acid concentration-time profiles were used to assess pharmacokinetics. Bioequivalence assessments were made via the 90% confidence interval for maximum plasma valproic acid concentration (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(infinity)). The relative bioavailability point estimates (90% confidence interval) for C(max) and AUC(infinity) were 1.05 (0.94-1.16) and 0.95 (0.83-1.09) under fasting conditions, and 1.01 (0.91-1.12) and 0.97 (0.87-1.08) under nonfasting conditions, respectively. The test 250 mg tablet formulation was bioequivalent to the reference 500 mg tablet formulation, under both fasting and nonfasting conditions, as the 90% confidence intervals for both C(max) and AUC(infinity) were within the 0.80-1.25 interval.