Model-Based Bioequivalence Analysis to Assess and Predict the Relative Bioavailability of Valproic Acid Formulations.

Background And Objective: Model-based bioequivalence (MBBE) encompasses the use of nonlinear mixed effect models supporting the estimation of pharmacokinetic endpoints to assess the relative bioavailability between multi-source drug products. This application emerges as a valuable alternative to the standard non-compartmental analysis (NCA) in bioequivalence (BE) studies in which dense sampling is not possible. In this work, we aimed to assess the application of MBBE compared to traditional methods in evaluating the relative bioavailability of two formulations with different drug release properties.

Quantitative systems pharmacology Model to characterize valproic acid-induced hyperammonemia and the effect of L-carnitine supplementation.

Valproic acid (VPA) is a short-chain fatty acid widely prescribed in the treatment of seizure disorders and epilepsy syndromes, although its therapeutic value may be undermined by its toxicity. VPA serious adverse effects are reported to have a significant and dose-dependent incidence, many associated with VPA-induced hyperammonemia. This effect has been linked with reduced levels of carnitine; an endogenous compound involved in fatty acid's mitochondrial β-oxidation by facilitation of its entrance via the carnitine shuttle.

Integration of in vitro biorelevant dissolution and in silico PBPK model of carvedilol to predict bioequivalence of oral drug products.

Bioequivalence implementation in developing countries where a high proportion of similar drug products are being marketed has found several obstacles, impeding regulatory agencies to move forward with this policy. Biopharmaceutical quality of these products, several of which are massively prescribed, remains unknown. In this context, an in vitro-in silico-in vivo approach is proposed as a mean to screen product performance and target specific formulations for bioequivalence assessment.