Avaliação da bioequivalência entre duas formulações de succinato de desvenlafaxina monoidratado ­ 50 mg comprimido revestido de liberação prolongada ­ administradas em jejum e pós-prandial em voluntários sadios de ambos os sexos / Bioequivalence evaluation of two desvenlafaxine succinate monohydrate formulations 50-mg extendedrelease coated tablet administered in fasted and fed conditions in healthy male and female volunteers

Objetivo: O objetivo deste trabalho foi avaliar a bioequivalência entre duas formulações de succinato de desvenlafaxina monoidratado 50 mg comprimido revestido de liberação prolongada, sendo a formulação teste produzida por Medley Farmacêutica Ltda. e a formulação referência (Pristiq™) comercializada por Wyeth Indústria Farmacêutica Ltda. Métodos: Os estudos foram conduzidos em voluntários sadios e as formulações administradas em dose única, sob o estado jejum e pós-prandial. Cada estudo foi conduzido de maneira independente, sendo ambos do tipo aberto, dois períodos, utilizando um delineamento do tipo crossover 2x2, envolvendo 48 voluntários, com intervalo de sete dias entre os períodos (washout). Resultados: Na administração em jejum, a razão entre a média geométrica da formulação teste e referência (T/R) de Cmáx foi 107,49%, com intervalo de confiança (IC) 90% de 100,81 a 114,60%. Para ASC0-t, a razão T/R foi de 104,90%, com IC 90% de 97,53 a 112,82%. Na administração pós-prandial, a razão T/R de Cmáx foi 103,17%, com IC 90% de 95,08 a 111,94%. Para ASC0-t, a razão T/R foi 103,40%, com IC 90% de 94,97 a 112,58%. Conclusões: As formulações teste e referência foram consideradas estatisticamente bioequivalentes em ambas as condições de administração, jejum e pós-prandial, de acordo com os critérios exigidos pela Agência Nacional de Vigilância Sanitária (Anvisa). A formulação teste foi o primeiro medicamento similar (Zodel®, 50 e 100 mg) registrado pela Anvisa nessa categoria e disponibilizado para comercialização, contribuindo assim com a ampliação da disponibilidade do tratamento para o transtorno depressivo maior e a redução de custos ao paciente.

Objective: The objective of this work was to evaluate the bioequivalence between two desvenlafaxine succinate monohydrate formulations 50-mg extended-release tablet, the test product manufactured by Medley Farmacêutica Ltd. and reference product (Pristiq™) commercialized by Wyeth Indústria Farmacêutica Ltda. Methods: The studies were performed in healthy volunteers and the formulations were administered in single-dose under fasted and fed conditions. Each study was conducted independently and performed of type open, two periods, using a 2x2 crossover design, involving 48 volunteers, with seven days of minimum interval between periods (washout). Results: In the fasted administration, the ratio between the geometrical mean of test formulation and reference (T/R) of Cmax was 107.49%, with confidence interval 90% (CI 90%) of 100.81 to 114.60%. For AUC0-t, the ratio T/R was of 104.90%, with CI 90% from 97.53% to 112.82%. In the fed administration, the ratio T/R of Cmax was 103.17% with CI 90% of 95.08 to 111.94%. For AUC0-t, the ratio T/R was 103.40%, with CI 90% of 94.97 to 112.58%. Conclusions: The test and reference formulations were considered statistically bioequivalent in the two administration conditions, fasted and fed, according to the requirements of Brazilian National Health Surveillance Agency (Anvisa). The test formulation was the first similar medicine (Zodel®, 50 e 100 mg) to be registered by Anvisa in this category and available to commercialization, thus contributing to increase the availability of treatment for major depressive disorder and the reduction of costs to the patient.

Incidence and anatomy of cardiac malformations in children conceived by assisted reproduction techniques - A review.

The aim of this study is to identify the occurrence of cardiac malformations occurred in children conceived by assisted reproduction techniques (ART) in the international literature in Medline database from 1999 to 2012. The search returned data on 32,000 births, whose 21,000 were conceived naturally and 11,000 were conceived by ICSI and/or IVF. The incidence of cardiac malformations in general population situations was 0.4%. The incidence of cardiac malformations by ART was 1.8% from ICSI and IVF. Among the situations of conceived naturally was observed 88 cases of cardiac malformations, which were: Atrial Septal Defect: 26 cases 29.55%, Change in the interventricular septum: 18 cases 20.45%, coarctation of the aorta: 13 cases 14.77%, aortic stenosis: 11 cases 12.5%, tetralogy of Fallot: 5.68% 5 cases, stenosis of the pulmonary trunk: 5 cases 5.68% other: 11.37% 10 cases. In cases of cardiac malformations in children conceived by IVF and ICSI, 198 cases were found, which were: CIA: 58 cases 29.30%, Change in the interventricular septum: 37 cases 18.69%, coarctation of the aorta: 20 cases 10.10%, aortic stenosis: 18 cases 9.09%, tetralogy of Fallot: 11 cases 5.55%, stenosis of the pulmonary trunk: 6 cases 3.03%, Other: 48 cases 24.24%. There remain opened questions about infertility and risk factors involving ART. Further research is clearly required. Health care providers should counsel infertile couples seeking assisted reproduction by IVF and technology.