Bioavailability comparison between a Chilean generic preparation of ambroxol and the original product Bioequivalencia de una formulación nacional de ambroxol

Objectives: To assess the relative bioavailability of two oral formulations of ambroxol commercialized in Chile, a generic syrup and the original product, Mucosolvan R from Boehringer Ingelheim. Methods: A randomized, cross-over and double blind study was performed in twelve healthy volunteers who received a single oral dose of either Mucosolvan (90 mg) or the generic formulation with at least a 14 day washout period between each single dose. Multiple blood samples were collected after each dose, the plasma ambroxol concentrations were determined by a validated High Performance Liquid Chromatography assay. Results: The 95% confidence intervals for all parameters were within the accepted range of 80-125% for bioequivalence, suggested by the US FDA. Non statistically significant differences were found in the mean parameters of bioequivalence: mean peak concentration (C max), area under the curve calculated from time zero to a determined time (AUC 0-t), and area under the curve calculate

Farmacovigilancia de vacunas y su aplicación en Chile

Resumen: La inmunización se encuentra entre las intervenciones en salud pública más exitosas y costo efectivas de todas las épocas, siendo su beneficio tan importante como su seguridad.Las vacunas, como cualquier otro medicamento, pueden generar eventos adversos, los que deben ser monitorizados permanentemente por sistemas de vigilancia. Esta disciplina recibe el nombre de Farmacovigilancia de Vacunas (FVV), encargada de estudiar los Eventos Supuestamente Atribuidos a la Vacunación ó Inmunización (ESAVI).El objetivo de este trabajo es revisar la evolución del sistema de farmacovigilancia de vacunas en Chile.El sistema de FVV chileno se basa en la vigilancia pasiva, y contempla la notificación obligatoria al Instituto de Salud Pública (ISP) de todos los ESAVI detectados, por parte de profesionales de la salud, directores de establecimientos y titulares de registro sanitario, priorizando las notificaciones de ESAVI serios e incluyendo la monitorización de todas las vacunas usadas en el país, tanto las que se encuentran incorporadas al Programa Nacional de Inmunización (PNI), como las que se encuentran fuera de este. El sistema de FVV chileno se caracteriza por un trabajo colaborativo permanente entre el ISP y el PNI, y parte de sus desafíos incluyen generar capacidades y alianzas estratégicas con la academia para la realización de estudios post comercialización sobre seguridad de vacunas.Finalmente, es importante destacar que tanto el marco normativo promulgado el año 2010, como la elaboración de procedimientos, el trabajo permanente con el PNI, y la conformación de un comité de expertos de ESAVI, y las diferentes estrategias de retroalimentación, son medidas implementadas que han contribuido a mejorar la tasa de reporte nacional y el análisis de los casos. Summary: Immunization is among the most successful and cost-effective public health interventions of all times, its benefits being as important as its safety.Vaccines, like any other medicine, can generate adverse events, which must be permanently monitored by surveillance systems. Vaccine Pharmacovigilance (VPV) is the discipline responsible for studying Adverse Events Following Immunization (AEFI).The objective of this article is to review the evolution of the pharmacovigilance system of vaccines in Chile.The Chilean VPV system is based on passive surveillance, and establishes the mandatory reporting of all AEFI detected by healthcare workers, directors of healthcare facilities, and Marketing Authorization holders, to the Public Health Institute of Chile (PHI), prioritizing the reporting of serious ESAVI and including the monitoring of all vaccines used in the country, both those that are incorporated into the National Immunization Program (NIP), and those that are outside of it. The Chilean VPV system is characterized by a permanent collaborative work between the PHI and the NIP, and its challenges include generating capacities and strategic alliances with the academy to carry out post-marketing studies on vaccine safety.Finally, it's important to point out that the regulatory framework promulgated in 2010, as well as the elaboration of procedures, the permanent work with the NIP, the formation of an AEFI expert committee, and the different feedback strategies implemented, have contributed in improving case analysis and the national reporting rate

Chile's National Advisory Committee on Immunization (CAVEI): Evidence-based recommendations for public policy decision-making on vaccines and immunization

A National Immunization Technical Advisory Group (NITAG) provides independent, evidence–based recommendations to the Ministry of Health for immunization programmes and policy formulation. In this article, we describe the structure, functioning and work processes of Chile's NITAG (CAVEI) and assess its functionality, quality of work processes and outputs, and integration of the committee into the Ministry of Health policy process using the Assessment tool for National Immunization Technical Advisory Groups. Among its strengths, CAVEI's administrative and work plasticity allows it to respond in a timely manner to the Ministry of Health's requests and proactively raise subjects for review. Representation of multiple areas of expertise within the committee makes CAVEI a robust and balanced entity for the development of evidence–based comprehensive recommendations. High ranking profile of the Secretariat structure furthers CAVEI's competences in policymaking and serves as a bridge between the committee and international initiatives in the field of immunizations

Early expression of monocyte chemoattractant protein-1 correlates with the onset of isoproterenol-induced cardiac fibrosis in rats with distinct angiotensin-converting enzyme polymorphism

Introduction. Isoproterenol treatment of Brown Norway Lewis rats (high and low plasma angiotersin-I-converting enzyme activity., respectively) results in similar cardiac hypertrophy but higher cardiac fibrosis in Brown Norway rats. Materials and methods. Rats were infused in vivo with isoproterenol for two or 10 days. Cardiac fibrosis and inflammation were evaluated histochemically. We measured the mRNAs of pro-fibrotic factors (transforming growth factor beta(1,) endothelin-1) and pro-inflammatory factors (monocyte chemoattractant protein-1). In studies with cardiac fibroblasts incubated with isoproterenol in vitro, we measured cell proliferation, angiotensin-I-converting enzyme and matrix metalloprotease 2 activities and deposition of collagen type I and fibronectin. Results. After treatment with isoproterenol for two days, there were large areas of myocardial injury and numerous inflammatory foci in the left ventricle, these being greater in Brown-Norway than in Lewis rats. After treatment with isoproterenol for 10 days, there were large areas of damage with extensive collagen deposition only in the left ventricle; both strains exhibited this damage which was, however, more severe in Brown-Norway than in Lewis rats. After treatment with isoproterenol for two, but not 10, days, greater amounts of monocyte chemoattractant protein-1 mRNA were found in Brown Nor-way than in Lewis rats. Cell proliferation, activities of angiotensin-I-converting enzyme and matrix metalloprotease 2,amounts of collagen type I and fibronectin were similar in cardiac fibroblasts from both strains; changes after isoproterenol (10 mu M) were also similar in both strains. Conclusion. We conclude that the greater cardiac fibrosis in Brown Norway rats treated with isoproterenol correlates with (lie early and higher expression of proinflammatory factors