ABSTRACT
Objective: To update information about drug interactions in patients with HIV/AIDS. Methods: Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. Results: Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. Conclusions: The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.
Objetivo: Actualizar información sobre interacciones medicamentosas en pacientes con VIH/SIDA. Métodos: Revisión estructurada en MEDLINE/PubMed utilizando los términos Mesh: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions, entre mayo de 2009 y diciembre de 2014. Publicaciones sobre interacciones medicamentosas, en humanos, en inglés o español y con acceso a texto completo fueron seleccionadas. Además, se incluyeron referencias de artículos considerados relevantes. La inclusión de los artículos fue evaluada por tres investigadores independientes y, en caso de requerirlo, por consenso entre ellos. La relevancia clínica se estableció en cuatro niveles, acorde con la gravedad y probabilidad de ocurrencia de la interacción. Resultados: Se identificaron 546 artículos, de los cuales se seleccionaron 273; además, se incluyeron 11 referencias relevantes. Se identificaron 935 parejas de interacciones medicamentosas, 95,7% farmacocinéticas. De este grupo, 823 mediadas por inducción o inhibición enzimática y 67 por cambios en la biodisponibilidad. De las 935 parejas de interacciones, 402 (43%) fueron relevantes clínicamente (niveles 1 o 2). Conclusiones: Las interacciones medicamentosas con anti-retrovirales de mayor relevancia clínica se deben a mecanismos farmacocinéticos, principalmente inducción o inhibición enzimática. Acorde con revisiones previas, los inhibidores de proteasa continúan siendo los anti-retrovirales con mayor número de interacciones relevantes.
Subject(s)
Humans , Acquired Immunodeficiency Syndrome/drug therapy , Anti-Retroviral Agents/pharmacokinetics , Drug-Related Side Effects and Adverse Reactions/etiology , Protease Inhibitors/pharmacokinetics , Risk Factors , Drug InteractionsABSTRACT
This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders.
O objetivo do presente estudo foi investigar a atividade anti-inflamatória in vitro de nanossuspensões e do complexo de inclusão contendo naproxeno. Esse fármaco é derivado de ácido propiônico, com ação analgésica, antipirética e antiinflamatória. A obtenção dessas formulações teve por finalidade o aumento da solubilidade e da atividade anti-inflamatória do fármaco. Os métodos por precipitação em solução aquosa por evaporação e por empastagem foram modificados para a obtenção da nanossuspensão e do complexo de inclusão, respectivamente. Para a avaliação da atividade anti-inflamatória das formulações utilizou-se ensaio in vitro modificado de inibição de tripsina. As propriedades físico-químicas das formulações propostas foram determinadas utilizando espectroscopia UV e de infravermelho, além de estudos de solubilidade. O complexo de inclusão de naproxeno apresentou menor atividade antitripsina, quando comparado ao composto livre e à nanossuspensão. Em conclusão, entre as formulações avaliadas, a nanossuspensão de naproxeno apresentou maior efeito anti-inflamatório. Esse efeito foi devido à redução da dimensão das partículas de naproxeno para a escala nanométrica. Com base nos resultados obtidos, a atividade da nanossuspensão de naproxeno foi notável. Dessa forma, essa formulação apresenta potencial para o tratamento de distúrbios inflamatórios.
Subject(s)
Protease Inhibitors/pharmacokinetics , Naproxen/pharmacokinetics , Solubility/drug effects , Excipients/pharmacokineticsABSTRACT
Aproximadamente 175 millones de personas están infectadas por el virus de la hepatitis C (VHC), lo que representa un 3% de la población mundial. En ausencia de tratamiento eficaz, un 25% de los pacientes desarrollan complicaciones hepáticas tras 25 años de hepatitis crónica C. Hasta hace poco, la única opción terapéutica en estos pacientes era la combinación de interferón pegilado (peg-IFN) y ribavirina (RBV). Alcanzaban la erradicación del VHC un 30-40% de los pacientes infectados con el genotipo 1 del VHC. Recientes avances han permitido desarrollar replicones y sistemas de cultivo tisulares para el VHC. Esto ha facilitado el diseño de fármacos antivirales directos (DAA) que inhiben específicamente la replicación del VHC. Los dos primeros inhibidores de la proteasa del VHC fueron aprobados en mayo de 2011. Permiten obtener tasas de curación en el 70% de los pacientes infectados con el genotipo 1 sin experiencia previa a interferón. La respuesta es menor en pacientes con fracasos previos, excepto en los recidivantes, en los que tasa de curación es del 90%...
Approximately 175 million people worldwide are chronically infected with the hepatitis C virus (HCV), representing 3% of the total world population. In the absence of successful therapy nearly 25% of these patients will develop hepatic complications within 25 years. Until recently, the only available therapeutic option for these patients was the combination of peginterferon-a plus ribavirin. Overall it allowed achievement of eradication in only 30-40% of patients infected by HCV genotype 1. The development of HCV replicons and the chance of producing infectious viral particles in culture systems have both enabled the rational design of direct-acting antivirals (DAA) that specifically inhibit HCV replication. The first two HCV protease inhibitors were marketed in May 2011. Triple therapy has increased the response rate to 70% in HCV genotype 1 carrier naïve to interferon. Although response rates are lower in prior failures, 90% sustained virological response rates are achieved in prior relapsers...