The aims of the proposed study were to develop and verify a quantitative model-based framework to anticipate the in vivo bioequivalence of ibuprofen immedi

The requirement for multiple-dose bioequivalence studies for the approval of generic prolonged-release (PR) formulations is not agreed upon by the EMA and FDA. While the EMA requests these studies, the FDA has no specific requirement, nor does ANVISA. Additional metrics are suggested for the assessment of prolonged-release products, and the partial Area Under the Curve (pAUC) metric has received increasing regulatory recognition. The objective of this work was to investigate whether the evaluation of the partial AUC in studies assessed by ANVISA can detect differences between 2 prolonged-release formulations that have demonstrated bioequivalence by the usual metrics. Twenty-four studies in a total of 117, which were already approved by ANVISA considering the usual metrics in the last 14 years, failed to demonstrate bioequivalence for partial AUC, which is related to 33.9% of evaluated PR products. For 76.92% of the studies, there was no significant increase in the intrasubject variability observed in the partial AUC analysis compared to the usual metrics, with a CV < 30% for both cases, calculated individually for each study, indicating that there is no need to increase the sample size to perform such analysis. The results of this paper demonstrate that the current criteria for assessing the bioequivalence of some prolonged-release formulations are insufficient and that the evaluation of partial AUC could be useful to assure the therapeutic parity of two products.

O objetivo deste trabalho consiste em identificar a existência de contágio financeiro utilizando a inovadora metodologia de Redes Bayesianas, executando-se uma análise sequencial. A análise da interdependência de mercados internacionais é realizada em períodos de crises financeiras, ocorridas entre os anos 1996 e 2009, envolvendo países nos quais foi possível avaliar seus efeitos e objetos de estudos similares na literatura. Os resultados apontaram para diversas evidências de contágio em períodos de crise, com causadores bem definidos. Por fim, verificou-se que, após as diversas crises, os mercados estavam muito mais interligados do que no período inicialmente adotado