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

Author(s)

Mendes, Gustavo D. ; Lotufo, Claudiney Cheli ; Bosio-Guimaraes, Renan Arthur ; de Castro, Heleson Alves ; Babadopulos, Tainah ; Ribas Freitas, Andre Ricardo ; Antunes, Natalicia de Jesus ; De Nucci, Gilberto

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS; v. 60, n. 5, p. 10-pg., 2022-05-01.

Abstract

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-max, AUC, t(max), Ke, and T-1/2. 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-max, 98.11% (90% CI = 94.66 - 101.70%) for AUC(last), and 96.71% (90% CI = 92.97 - 100.60%) for AUC(0-inf). Conclusion: Since the 90% CI for C-max and AUC(last) 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. What is known about this subject - Pharmacokinetic parameters have a wide variation. There are many methods of quantification. What this study adds - We present an analytical method suitable for the quantification of large numbers of samples. - The pharmacokinetic parameters between men and women under fasting conditions are compared. (AU)

• FAPESP's process: 19/16805-4 - Evaluation of the pathophysiological role of endothelial catecholamines
• Grantee: Gilberto de Nucci
• Support Opportunities: Research Projects - Thematic Grants