La calidad de los medicamentos genéricos/multifuentes (MG) debe ser garantizada por estudios de bioequivalencia (BE) en armonía con las directrices de la OPS/OMS, favoreciendo su acceso y fortaleciendo las Políticas de Medicamento Genéricos (PMG). La presente investigación tuvo por objetivo evaluar la reglamentación de los MG en América Latina y Europa, y la implementación de BE como requisito de su calidad. Metodología: Documentos oficiales normativos y reglamentarios de PMG, y guías de BE fueron evaluados mediante el metanálisis. Resultados: en América Latina; México y Brasil aplican la BE como requisito de calidad e intercambiabilidad de MG; Argentina, Colombia, Chile y Colombia en fármacos de riesgo sanitario elevado, el Perú actualmente lo ha incorporado para el registro de MG, quedando por definir el listado de los medicamentos con BE. Se discute sobre los requisitos legales y el impacto de la BE sobre las prestaciones farmacéuticas favoreciendo la incorporación de MG, seguros, eficaces y de bajo costo. La investigación valida la BE como requisito mínimo exigible para su registro, y comercialización de la fenitoina, carbamacepina, acido valproico y ciclosporina en el sistema sanitario peruano. Los fármacos de Clase I no requieren los estudios de BE y pueden solicitar su bioexcención. Palabras clave: Medicamento Genérico/multifuente, Bioequivalencia, Legislación de medicamentos / The quality of generic / multisource (MG) should be guaranteed by bioequivalence (BE) in harmony with the guidelines of the PAHO / WHO, promoting and strengthening their access generic drug policy (PMG). The present investigation was to evaluate the regulation of GM in Latin America and Europe, and the implementation of BE as a condition of its quality. Methodology: Official documents of the PMG policy and regulatory, and BE guidelines were evaluated using meta-analysis. Results: In Latin America, Mexico and Brazil applied the BE as a requirement of quality and interchangeability of MG, Argentina, Colombia, Chile and Colombia in high health risk drugs, Peru currently has built for the registration of MG, to be defined The list of drugs with BE. It discusses the legal requirements and the impact of BE on the pharmaceutical benefits by promoting the incorporation of MG, safe, effective and inexpensive. The research validates the BE as a minimum requirement for registration and marketing of phenytoin, carbamazepine, valproic acid and cyclosporine in the Peruvian health system. Class I drugs do not require BE studies and may apply for bioexcención. Keywords: Generic/Multisource Drugs, Bioequivalence, Drug Regulation

El presente trabajo desarrolla la validación prospectiva de una forma farmacéutica sólida cuyos principios activos contenidos son Rosiglitazona y Glimepiride, de tal modo que se demostró y estableció evidencia documentada que el proceso de análisis cumple de manera robusta y repetitiva lo que estaba previsto basado protocolo planificado, llamado protocolo de validación, obtenido de la secuencia de desarrollo del nuevo producto y de la metodología de análisis. En la parte inicial de este trabajo se procede a recopilar toda la información bibliografica necesaria para luego proceder con los primeros análisis exploratorios. Inicialmente con la intención de cuantificar ambos principios activos mediante un solo sistema cromatográfico, no obteniendo resultados esperados, seguidamente se procedió a probar sistemas cromatográficos diferentes para cada principio activo obteniendo los resultados adecuados para obtener la metodología analítica correcta. Una vez establecidas las condiciones cromatográficas finales con los parámetros definidos para el trabajo, se ejecuta el protocolo de validación del método desarrollado para lo cual se cuenta con el diseño experimental y los procedimientos estadísticos, concluyendo que la metodología analítica propuesta es lineal, exacta, y selectiva, cumpliendo así con los parámetros de validación establecidos en las obras oficiales; por lo cual el método validado es confiable y puede ser empleado en los análisis de rutina. / The present work develops the Prospective Validation of a Solid Pharmaceutical Form, which drogs are Rosiglitazone and Glimepiride, in such a way that it was demonstrated and established documented evidence that the process of analysis fulfills in a robust and repetitive way what there was foreseen based planned protocol, so-called Protocol of Validation, obtained of the sequence of development of the new product and of the methodology of analysis. At the first part of this work, all the bibliographical necessary information is proceeded to compile then to proceed with the first exploratory analyses. Initially with the intention of quantifying both active beginning by means of only one system cromatographic, not obtaining awaited results, then it was proceeded to prove in different system cromatographics by the every active beginning obtaining the results adapted to obtain the analytical correct methodology. As soon as the last conditions cromatographic were established with the parameters defined for the work, there is executed the Protocol of Validation the method developed for which is counted by the experimental design and the statistical procedures, concluding that the analytical proposed methodology is linear, exact, and selective, expiring this way with the parameters of ratification established in the official works; for which the validated method is reliable and can be used in the analyses of routine.

Se desarrolló una técnica analítica por cromatografía liquida de alta performance (HPLC) para cuantificar los principios activos clonixinato de lisina y pargeverina clorhidrato en tabletas recubiertas, debido a que la técnica de análisis para este medicamento compuesto no se encuentra en libros oficiales. La técnica de análisis para ambos principios activos es realizada en un solo sistema (fase móvil, columna cromatográfica, longitud de onda), diferenciándose sólo en la preparación de la muestra y el volumen de inyección por lo que no pueden ser cuantificadas en un solo cromatograma, debido a la gran diferencia de sus concentraciones en la tableta y sus propiedades de solubilidad. Previamente a la validación se evaluó la aptitud del sistema. Los resultados fueron conformes a las especificaciones para un método cromatográfico recomendadas por la USP 30, comprobando que el equipo, el sistema electrónico, las operaciones analíticas y las muestras a analizar constituyen un sistema integral que puede evaluarse como tal. Para la validación se evaluaron los parámetros de desempeño de la técnica como son: Selectividad, Exactitud, Precisión, Precisión Intermedia, Linealidad y Rango. Los resultados de estos parámetros se sometieron a pruebas estadísticas demostrando que la técnica analítica propuesta para la cuantificación de los principios activos es selectiva, exacta, precisa y lineal, así mismo la confiabilidad de la nueva técnica, garantizando de esta forma la calidad, eficacia e inocuidad del medicamento. / An analytical technique by high performance liquid chromatography (HPLC) was developed to quantify the active principles lysine clonixinate and pargeverine chlorhidrate in covered tablets, because the technique of analysis for this compound medicine is not in official books. The technique of analysis for both active principles is made in a single system (movable phase, chromatographic column, wavelength), being different itself only in the sample preparation and the volume of injection reason why cannot be quantified in a single chromatogram, due to the great difference of their concentrations in the tablet and its properties of solubility. Previously to the validation the aptitude of the system was evaluated. The results were in agreement to the specifications for a chromatographic method recommended by the USP 30, verifying that the equipment, the electronic system, the analytical operations and the samples to analyze constitute an integral system that can be evaluated like so. For the validation the parameters of performance of the technical were evaluated as they are: Selectivity, Accuracy, Precision, Intermediate Precision, Linearity and Range. The results of these parameters were also put to the test statistical demonstrating that the proposed analytical technical for the quantification of the active principles is selective, exact, precise and linear, to the trustworthiness of the new technical, guaranteeing of this form the quality, effectiveness and harmlessness of the medicine.

El análisis por HPLC, de productos farmacéuticos son una necesidad y de uso rutinario. Esta técnica evita errores que conllevan a situaciones de riesgo al usuario, garantizando que la dosis prescrita llegue al paciente en la cantidad apropiada. En la rutina de laboratorio reduce repeticiones analíticas y facilita mayor rapidez en los análisis que adecuadamente validadas dan confiabilidad a los resultados. Las farmacopeas vigentes contemplan en la mayoría de los casos análisis por HPLC para monofármacos o asociaciones de dos o más principios activos por separado lo cual demanda un mayor tiempo de análisis y un mayor costo. La validación es el proceso establecido para la obtención de pruebas documentadas y demostrativas de que un método de análisis es lo suficientemente fiable y reproducible para producir el resultado previsto dentro de los intervalos definidos. La validación de un método analítico es un requisito necesario para cumplir con las Buenas Prácticas de Manufactura (BPM) y así asegurar la calidad del medicamento. El presente trabajo plantea el uso de un solo método analítico por HPLC para un producto farmacéutico en presentación de Crema que contiene en su formulación dos principios activos: Clotrimazol y Dexametasona Acetato, los cuales se determinan en un solo análisis, el cual seguidamente fue validado para determinar así la aplicabilidad del método. En la validación del método analítico se evaluaron una serie de parámetros que están indicados en obras oficiales, como son: selectividad, linealidad, precisión, exactitud y robustez. Posteriormente, se elaboró el Protocolo de validación del método de análisis, para lo cual se contó con el diseño experimental y los procedimientos estadísticos, concluyéndose así que el método analítico propuesto es selectivo, lineal, preciso, reproducible y exacto; y de esta manera comprobamos la validez del método analítico desarrollado. / The analysis for HPLC of pharmaceutical products is a necessity and of routine use. This technique avoids mistakes that make risk situations to user, guaranteeing that the prescribed dose arrives at the patient in the appropriate amount. In the laboratory routine it reduces analytical repetitions and it facilitates greater rapidity in the analysis that suitably validated give trustworthiness to the results. The effective pharmacopeias contemplate in the most of the cases analysis for HPLC, for monodrugs o associations of two or more actives principles which demands a greater time of analysis and greater cost. The validation is the process established for the obtaining of documented and demonstrative tests that an analysis method is the sufficiently trustworthy and reproducible for produce the result anticipated inside the defined intervals. The validation of an analytical method is a requirement necessary to fulfill the Good Practices Manufacture (BPM) and thus to assure the quality of medicament. The present work shows the use of a single analytical method for HPLC for a pharmaceutical product in cream presentation that contains in its formulation two actives principles: Clotrimazole and Dexamethasone acetate, which are determined in a single analysis, which after was validated to determine thus the applicability of the method. In the validation of analytical method a series of parameters was evaluated that are indicated in official works, as they are: selectivity, linearity, precision, exactitude and robustness. Later, the Protocol of Validation of analysis method was elaborated, for which it counted on the experimental design and the statistical procedures, concluding so the proposed analytical method is selective, linear, precise, reproducible and exact; and this way we verified the validity of developed analytical method.

La validación del proceso de fabricación de las tabletas de glibenclamida 5mg, fue realizado en un laboratorio farmacéutico, durante los meses de marzo a octubre del 2005. En este período se llevó a cabo la fabricación de tres lotes consecutivos, los cuales fueron utilizados para la validación. El estudio nos permitió demostrar que la validación del proceso de fabricación de las tabletas de glibenclamida 5mg cumplió con los parámetros establecidos. Demostrándose que los equipos, etapas y las áreas estaban adecuadamente instaladas, documentadas y operativas tal como se evidenció de manera consistente y repetitiva durante todo el proceso de validación. Adicionalmente los datos obtenidos del proceso de fabricación de las tabletas de glibenclamida 5 mg; fueron procesados con el paquete estadístico SPSS 11.10; demostrándose que existe diferencia significativa con un p < 0,05 entre el inicio, medio y final de los tres lotes. Por tanto se concluye que el proceso cumplió con las especificaciones establecidas, pero no asegura que estadísticamente este bajo control; porque las herramientas estadísticas nos permitieron evaluar con un alto grado de confiabilidad el comportamiento real del proceso. / The validation of the manufacturing process of the tablets glybenclamide 5mg, was carried out in a pharmaceutical laboratory, during the months of March to October of the 2005. In this period was carried out the production of three serial lots, which were used for the validation. The study allowed us to demonstrate that the validation of the manufacturing process of the tablets glybenclamide 5mg completed the established parameters. Being demonstrated that the equipment, stages and the areas were appropriately installed, documented and operative just as it was evidenced in a consistent and repetitive way during the whole validation process. Additionally the obtained data of the manufacturing process of the tablets of glybenclamide 5 mg; they were processed with the statistical package SPSS 11.10; being demonstrated that significant difference exists with a p < 0,05 among the beginning, means and end of the three lots. Therefore you concludes that the process completed the established specifications, but it doesn't assure that statistically this low control; because the statistical tools allowed us to evaluate with a high grade of dependability the real behavior of the process.

Se realizó un estudio de tipo descriptivo-longitudinal prospectivo de la incidencia de reacciones adversas a medicamentos en pacientes hospitalizados en el Servicio de Emergencia del Hospital Nacional Guillermo Almenara Irigoyen durante el periodo enero-marzo 2003. Se analizaron 865 casos de pacientes hospitalizados en dicho servicio para determinar la existencia de reacciones adversas a medicamentos (RAM) detectándose 67 pacientes con casos de RAM obteniéndose una incidencia de 7.75%, presentándose mayormente en pacientes varones entre 75-93 años y 56-74 años de edad; las reacciones fueron moderada en el 53.52% de los casos. Los principales grupos terapéuticos implicados fueron: antibióticos (23.94%), AINES (16.9%) y antihipertensivos (8.45%) y los órganos y sistemas más afectados se destacan el tracto gastrointestinal (22.54%) y el sistema cardiovascular (14.08%). / A descriptive-longitudinal prospective study of incidence of Drug adverse reaction in patients hospitalized in Emergency facility of Guillermo Almenara Irigoyen national hospital during January to march 2003 of was carried out. It was analizad 865 cases of hospitalized patients in that facility during three months in order to determine the existence of drug adverse reactions (DAR's), from those ones, it was detected 67 patients with cases of DAR's, having obtained an incidence of 7.75%, particularly presented in male patients and between 75-93 years old and 56-74 years old; DAR's were moderate in the 53.52% of the cases. The principal therapeutic groups implied were: antibiotic (23.94%), NON-Sterroidal anti-inflammatory (16.9%) and anti-hypertensive (8.45%) drugs and the organs and systems more affected, it was highlighted, gastrointestinal tract (22.54%) and cardiovascular system (14.08%).

El Sistema de Distribución de Medicamentos por Dosis Unitaria (SDMDU) permite un adecuado seguimiento farmacoterapéutico de los pacientes, integra al farmacéutico al equipo asistencial y produce un significativo ahorro económico al hospital. En el presente estudio se diseñó como objetivos: cuantificar el porcentaje de devolución e identificar los grupos terapéuticos de mayor consumo y devolución producido por el SDMDU en el periodo 2003-2004. Además, identificar los errores al analizar las recetas médicas atendidas por el SDMDU y conocer la participación del farmacéutico en el sistema. El método consistió en un análisis retrospectivo-descriptivo de las recetas médicas, reportes de consumo-devolución y encuestas dirigidas al equipo de salud. Los resultados obtenidos nos muestran que el costo total de medicamentos y material biomédico fue de S/. 3 046 014.77; las devoluciones sumaron S/. 171 634.14. El grupo terapéutico de mayor consumo fueron los antibacterianos con 47% y una devolución de 44%. Los principales tipos de errores encontrados fueron: datos incompletos del paciente 77%, datos en la prescripción 37% y errores de dispensación 19%. La mayoría de profesionales opinaron que el farmacéutico tiene una participación poco activa al integrarse al equipo de salud. Se concluye que: el porcentaje de devolución en el periodo de estudio fue de 6% y en el funcionamiento del SDMDU se encontraron fallas en el sistema, tales como: deficiencias en el suministro de medicamentos, errores de dispensación, falta de seguimiento farmacoterapéutico y la participación poca reconocida de los farmacéuticos. / The Unit Dose Drug Distribution System (SMDUD) permits an adequate pharmacotherapeutic tracking in the patients, integration of the pharmacist to health’s team and it produces an important economic saving to the hospital. Our study it was designed as objectives: quantifying the devolution percents and identifying the therapeutic groups of bigger consumption and devolution, produced for the SDMDU in the period 2003-2004. Furthermore, identifying errors at examining the medical prescriptions attended for the SDMDU and know the participation of the pharmacist in the system. The method consisted in a retrospective-descriptive analysis of the medical prescriptions, reports of consumption-devolution and surveys guided to the team of health. The results obtained show that the total cost of medicaments and biomedical material were S/. 3 046 014.77, and the devolutions summed up S/. 171 634.14. The therapeutic groups of bigger consumption were the antibacterials with 47% and his devolution of 44%. The principal types of errors found were: the patient's incomplete data 77%, data in the prescription 37% and errors of dispensation 19%. Most of professionals opine that the pharmacist has a little active participation when he integrates to the team of health. It is concluded that: the devolution percents in the period of study went from 6% and in the SDMDU's functioning it is finding faults; thus as, in the provision of medications, errors of dispensation, lack of pharmacotherapeutic tracking and the little recognize participation of the pharmacists.

Made available in DSpace on 2013-08-07T19:03:39Z (GMT). No. of bitstreams: 1 000446130-Texto+Completo-0.pdf: 1910036 bytes, checksum: 59d877dc63ef59118f780b6e08cf8f9f (MD5) Previous issue date: 2012 / Tuberculosis remains the most common cause of death due to an infectious agent. Among targets identified in Mycobaterium tuberculosis genome, enzymes of the shikimate pathway deserve special attention. Shikimate kinase is the fifth enzyme of the shikimate pathway, which has been identified in fungi, apicomplexans, plants and prokaryotes. This metabolic route is composed of seven steps, which converts erythrose-4-phosphate and phosphoenol pyruvate to chorismic acid and is responsible for the biosynthesis of aromatic amino acids. Shikimate kinase has been shown to be essential to the survival of Mycobacterium tuberculosis, and since it is absent in human, this enzyme is considered to be a target for chemotherapeutic for development of antitubercular drugs. The aim here is to identify possible inhibitors, focusing on simulations of molecular docking in the ATP-binding site of the enzyme. The program used in the simulations was the Molegro Virtual Docker and protein-ligand interactions were tested in 12 crystallographic structures and then, it was choosen a protocol which generated docking RMSD values below 2 Å. Application of this docking protocol to a decoy dataset generated a enrichment factor of 24. 57, which is considered adequate for molecular docking simulations focused on kinases. The present docking protocol was then applied to a small-molecule database with over 80,000 entries. Analysis of the results identified 5 potencial shikimate kinase inhibitors. Examination of the intermolecular interaction between enzyme and the ligands identified the main structural features responsible for ligand-binding affinity. This is the first molecular docking study focused on the ATP-binding pocket of shikimate kinase. / A Tuberculose continua sendo a causa mais comum de morte em decorrência de um agente infeccioso. Entre os alvos identificados no genoma do Mycobaterium tuberculosis, enzimas da via do chiquimato merecem atenção especial. A chiquimato quinase é a quinta enzima da via do chiquimato, e tem sido identificada em fungos, organismos do filo apicomplexa, plantas e procariontes. Esta via metabólica é composta por sete passos, que catalisam sequencialmente a conversão de eritrose-4-fosfato e fosfoenolpiruvato em corismato; e é responsável pela biossíntese de aminoácidos aromáticos. Chiquimato quinase parece ser essencial para a sobrevivência do Mycobacterium tuberculosis, uma vez que é ausente no homem, esta enzima é considerada como um alvo para o desenvolvimento de quimioterápicos e medicamentos contra a tuberculose. O objetivo é identificar possíveis inibidores, focando as simulações de docking molecular no sítio de ligação do ATP da enzima. O programa usado nas simulações foi o Molegro Virtual Docker e a interação proteína-ligante foi testada em 12 estruturas cristalográficas e logo após, escolhido um protocolo de docking a partir de valores de RMSD abaixo de 2Å. O método foi validado usando o melhor protocolo de re-docking no Virtual Screening através do Fator de Enriquecimento que obteve resultado de 24,57%, que é considerado adequado para as simulações de docking molecular focados em quinases. O presente protocolo de docking foi aplicado em um banco de dados com mais de 80. 000 moléculas. A análise dos resultados identificaram 5 potenciais inibidores da chiquimato quinase. Na análise das interações intermoleculares entre a enzima e os ligantes foram identificadas características estruturais responsáveis pela afinidade da ligação pelo ligante. Este é o primeiro estudo de docking molecular focado no bolsão de ligação do ATP da chiquimato quinase.

Made available in DSpace on 2013-08-07T19:05:02Z (GMT). No. of bitstreams: 1 000439097-Texto+Completo-0.pdf: 7980733 bytes, checksum: af8f6a7fa6a599651957ad5f12054783 (MD5) Previous issue date: 2012 / Tuberculosis continues to be one of the deadliest diseases in the world. The emergence of drug-resistant strains of Mycobacterium tuberculosis, the unbearable side effects of the available drugs and the frequent patient non-compliance in completing the therapy have increased the need for development of new effective agents. We have previously demonstrated a potent in vitro inhibitory activity for two pentacyano(isoniazid)ferrate(II) compounds, namely IQG-607 and IQG-639 against the M. tuberculosis enoyl-ACP reductase enzyme. Importantly, IQG- 607 and IQG-639 were active against cultures of M. tuberculosis H37Rv and two isoniazid-resistant clinical isolates in vitro. In the present study, the activity of these compounds was evaluated by using an in vivo murine model of tuberculosis. Swiss mice were infected with M. tuberculosis H37Rv strain, and IQG-607 and IQG-639 (250 mg/kg) were administered during 28 or 56 days. As well, a dose-response study was performed with IQG-607 (at 5, 10, 25, 50, 100, 200 and 250 mg/kg). The activity of test compounds was compared with that of the positive control drug isoniazid at 25 mg/kg. After 28 or 56 days of treatment, either IQG-607 or isoniazid significantly reduced M. tuberculosis-induced splenomegaly, and also significantly diminished the colony-forming units in both spleens and lungs. IQG-607 or isoniazid ameliorated the lung macroscopic aspect, reducing the lung lesions to a similar extent. However, IQG-639 was not capable of significantly modifying any evaluated parameter. IQG-607 did not display a classical dose-dependent profile in our murine model of tuberculosis, and 10 mg/kg was the lowest dose able to show significant activity, which was similar to the inhibition observed for higher doses. In addition, experiments using early and late controls of infection revealed a bactericidal activity for IQG-607 in our model. The promising activity of IQG-607 in M. tuberculosis-infected mice suggests that this compound might represent a good candidate for clinical development as a new antimycobacterial agent. / A tuberculose é uma das principais causas de morte no mundo. O surgimento e disseminação de cepas de Mycobacterium tuberculosis resistentes a fármacos, os efeitos indesejáveis dos fármacos atualmente disponíveis e a falta de adesão dos pacientes ao tratamento têm aumentado a necessidade do desenvolvimento de novos agentes anti-tuberculose. Estudos prévios revelaram uma potente atividade inibitória in vitro de dois compostos pentaciano(isoniazida)ferrato(II), denominados IQG-607 e IQG- 639, frente a enzima enoil-ACP redutase de M. tuberculosis. Ainda, o IQG- 607 e o IQG-639 foram ativos quando testados em culturas de M. tuberculosis H37Rv e sobre dois isolados clínicos resistentes à isoniazida in vitro. Neste trabalho, a atividade destes dois compostos foi avaliada in vivo, utilizando um modelo murino de infecção por M. tuberculosis. Camundongos suíços foram infectados com a cepa de M. tuberculosis H37Rv e o IQG-607 ou o IQG-639 (250 mg/kg) foram administrados aos animais durante 28 ou 56 dias. Adicionalmente, um estudo de dose-resposta foi realizado com o composto IQG-607, empregando as doses de 5, 10, 25, 50, 100, 200 e 250 mg/kg. As atividades dos compostos-teste foram comparadas à atividade da isoniazida (25 mg/kg), o controle positivo do tratamento. Após 28 ou 56 dias de tratamento, tanto o IQG-607 quanto a isoniazida reduziram significativamente a esplenomegalia induzida pela infecção e, também, diminuíram as unidades formadoras de colônia, tanto nos pulmões quanto nos baços dos animais tratados. O IQG-607 e a isoniazida melhoraram o aspecto macroscópico dos pulmões, reduzindo as lesões pulmonares de maneira semelhante. Por sua vez, o IQG-639 não foi capaz de modificar significativamente nenhum parâmetro avaliado neste estudo. O IQG-607 não apresentou um perfil clássico de dose dependência, sendo observada atividade inibitória significativa similar, entre as doses de 10 mg/kg e 250 mg/kg. Além disto, um experimento utilizando um “controle pré-tratamento” demonstrou que o IQG-607 possui atividade bactericida no nosso modelo. A atividade satisfatória do IQG-607 em camundongos infectados com M. tuberculosis sugere que este composto pode ser um candidato promissor no desenvolvimento clínico de um novo agente antimicobacteriano.

Made available in DSpace on 2013-08-07T18:42:06Z (GMT). No. of bitstreams: 1 000432437-Texto+Completo-0.pdf: 10723389 bytes, checksum: d0fa4e1abb05919515c5199dcf4ecc73 (MD5) Previous issue date: 2011 / The inhA gene from Mycobacterium tuberculosis (Mtb), encodes for an enoyl acyl carrier protein reductase, InhA, a key enzyme of the mycobacterial type II fatty acid elongation cycle and has been validated as an effective target for the development of anti-microbial agents. InhA catalyzes the NADH-dependent reduction of trans double bond between positions C2 and C3 of fatty acyl substrates. It is the target of isoniazid, a first line drug in the tuberculosis treatment. Mutations in InhA structural gene are associated with isoniazid resistance in vivo. Even though mutations within the inhA gene are known to facilitate isoniazid resistance, InhA remains a good candidate for drug design because: (i) the vast majority of the mutations found in isoniazid-resistant clinical isolates are associated with the isoniazid activator (KatG catalase-peroxidase); (ii) only one enoyl-ACP reductase is found in Mtb, unlike some of the other enzymes of bacterial FAS-II systems; (iii) the longer substrate chain length specificity of InhA distinguishes it from the enoyl-ACP reductases from other sources. Our goal with this work was to analyze in detail the structural and physicochemical available information about Mtb InhA using bioinformatics tools. As a result, we developed a pharmacophoric model based on the InhA substrate binding cavity that allowed the application of a virtual screening methodology focused in selecting ligands that satisfied these features, allowing so, a best complementarity with the target protein. Besides we tested the hability of four docking algorithms to find similar conformation to a molecule, providing clues that this would be the conformation closest that adopted in vivo. Finally, molecular dynamics simulations were employed to achieve a better comprehension of the interaction between InhA and a known inhibitor. / O gene inhA de Mycobacterium tuberculosis (Mtb) codifica a enzima enoil redutase, InhA, uma enzima chave no ciclo de alongamento de ácidos graxos tipo II e têm sido validada como um alvo efetivo para o desenvolvimento de agentes antimicrobianos. A InhA catalisa a redução NADH-dependente da ligação dupla trans entre as posições C2 e C3 de substratos de ácidos graxos. Ela é o alvo da isoniazida, uma droga de primeira linha no tratamento da tuberculose. Mutações no gene estrutural da InhA estão associadas com a resistência à isoniazida in vivo. Mesmo que mutações no gene inhA sejam conhecidas por facilitar a resistência à isoniazida, InhA ainda é uma excelente candidata a alvo para o planeamento de fármacos porque: (i) a grande maioria das mutações encontradas em isolados clínicos de cepas resistentes à isoniazida estão associadas com o ativador da isoniazida (KatG catalase-peroxidase); (ii) apenas uma enoil-ACP redutase é encontrada em M. tuberculosis, ao contrário de outras enzimas dos sistemas FAS-II de bactérias; (iii) a especificidade da InhA por substratos de cadeia mais longa a distingue das enoil-ACP redutases de outros tipos. Nosso objetivo com este trabalho foi de analisar em detalhe as informações estruturais e físico-químicas disponíveis sobre a InhA de Mtb utilizando ferramentas de bioinformática. Como resultado, foi desenvolvido um modelo farmacofórico baseado na estrutura do sítio de ligação ao substrato da InhA, permitindo a aplicação de uma metodologia de triagem virtual focada em selecionar ligantes que satisfizessem essas características, permitindo assim, a melhor complementariedade com a proteína alvo. Além disso testamos a habilidade de quatro algoritmos de docagem molecular em encontrar conformações semelhantes para uma mesma molécula, fornecendo indícios de que esta seja a conformação mais próxima àquela adotada in vivo. Por fim, simulações de dinâmica molecular foram empregadas para melhor compreensão da interação da enzima InhA com um inibidor já conhecido desta enzima.