Comparative bioavailability study with two sodium valproate tablet formulations administered under fasting conditions in healthy subjects.

AIM

To assess the bioequivalence of two sodium valproate formulations in healthy subjects of both sexes.

MATERIALS AND METHODS

The study was conducted using an open, randomized, two-period crossover design with a 2-week washout interval. Plasma samples were obtained over a 96-hour period. Plasma concentrations of valproate were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC/MS) with negative ion electrospray ionization. From the sodium valproate plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained C, AUC, t, Ke, and T.

RESULTS

The geometric mean with corresponding 90% confidence interval for test/reference percent ratios were 104.43% (90% CI 100.42 - 108.61%) for C, 98.11% (90% CI = 94.66 - 101.70%) for AUC, and 96.71% (90% CI = 92.97 - 100.60%) for AUC.

CONCLUSION

Since the 90% CI for C and AUC ratios were all inside the 80 - 125% interval proposed by the US Food and Drug Administration Agency (FDA), it was concluded that the new sodium valproate formulation (epilenil 500-mg coated tablet) without food elaborated by Biolab Sanus Farmaceutica Ltda is bioequivalent to depakene formulation for both the rate and the extent of absorption.