http://sedici.unlp.edu.ar:80/handle/10915/225 Mon, 19 Oct 2026 17:59:59 GMT 2026-10-19T17:59:59Z http://sedici.unlp.edu.ar:80/handle/10915/7863 Revision Hormesis: Background and implication in the biological systems Latin American Journal of Pharmacy; vol. 28, no. 6 A partir de la especialización que han experimentado algunas ramas de la ciencia, consecuencia del desarrollo científico, surgieron diferentes términos para denominar un mismo efecto. La hormesis como relación dosis-respuesta agrupa en un único concepto fenómenos que aparecen en todo el espectro biológico. En este artículo se hace un análisis sobre el origen de dicho concepto, las limitaciones que ha tenido su generalización, sus características como fenómeno biológico y manifestaciones en la vida diaria.; Specialization of some branches of science due to the scientific development resulted in the rise of different terminology to refer to the same effect. Hormesis is a dose-response relationship encompassing in a single concept several biological phenomena. This article provides an analysis of the origin of hormesis and the limitations of generalizing this concept. It also describes the main features of hormesis as a biological phenomenon, and its manifestations in daily life. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7863 2009-01-01T00:00:00Z A partir de la especialización que han experimentado algunas ramas de la ciencia, consecuencia del desarrollo científico, surgieron diferentes términos para denominar un mismo efecto. La hormesis como relación dosis-respuesta agrupa en un único concepto fenómenos que aparecen en todo el espectro biológico. En este artículo se hace un análisis sobre el origen de dicho concepto, las limitaciones que ha tenido su generalización, sus características como fenómeno biológico y manifestaciones en la vida diaria. Specialization of some branches of science due to the scientific development resulted in the rise of different terminology to refer to the same effect. Hormesis is a dose-response relationship encompassing in a single concept several biological phenomena. This article provides an analysis of the origin of hormesis and the limitations of generalizing this concept. It also describes the main features of hormesis as a biological phenomenon, and its manifestations in daily life. http://sedici.unlp.edu.ar:80/handle/10915/7862 Revision Electrochemical methods used for evaluation of antioxidant activity of natural products Latin American Journal of Pharmacy; vol. 28, no. 6 O presente artigo apresenta uma revisão sobre as aplicações dos métodos eletroquímicos na identificação e quantificação da atividade antioxidante. Trabalhos descrevendo o uso de técnicas voltamétricas (cíclica e de pulso diferencial), coulometria e sistemas de separação com detecção eletroquímica, utilizando diferentes tipos de eletrodos (ex. Pt, carbono vítreo, pasta de carbono), assim como técnicas combinadas (CRAC, biossensor de DNA) foram compilados. Uma breve leitura sobre grande quantidade de trabalhos descritos demonstra que é necessário estabelecer critérios de medida bem definidos que permitam comparações entre diferentes resultados. Sobre este aspecto, a padronização dos procedimentos de medida é ainda necessária.; This article presents a review about the application of electrochemical methods in the identification and quantification of antioxidant activity. Reports describing the utilization of voltammetry (cyclic and differential pulse), coulometry and amperometric detection systems, using the most different types of electrodes such as Pt, glassy carbon, pyrolitc graphite, carbon paste, chemical modified electrodes and biosensors, as well combined techniques (CRAC, DNA biosensor) were compiled. A brief reading over the enormous quantity of the reported data makes possible to conclude that it is necessary to get a measure criterion which allows the comparison between different results. Under this aspect, the standardization of the measurement procedures still is necessary. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7862 2009-01-01T00:00:00Z O presente artigo apresenta uma revisão sobre as aplicações dos métodos eletroquímicos na identificação e quantificação da atividade antioxidante. Trabalhos descrevendo o uso de técnicas voltamétricas (cíclica e de pulso diferencial), coulometria e sistemas de separação com detecção eletroquímica, utilizando diferentes tipos de eletrodos (ex. Pt, carbono vítreo, pasta de carbono), assim como técnicas combinadas (CRAC, biossensor de DNA) foram compilados. Uma breve leitura sobre grande quantidade de trabalhos descritos demonstra que é necessário estabelecer critérios de medida bem definidos que permitam comparações entre diferentes resultados. Sobre este aspecto, a padronização dos procedimentos de medida é ainda necessária. This article presents a review about the application of electrochemical methods in the identification and quantification of antioxidant activity. Reports describing the utilization of voltammetry (cyclic and differential pulse), coulometry and amperometric detection systems, using the most different types of electrodes such as Pt, glassy carbon, pyrolitc graphite, carbon paste, chemical modified electrodes and biosensors, as well combined techniques (CRAC, DNA biosensor) were compiled. A brief reading over the enormous quantity of the reported data makes possible to conclude that it is necessary to get a measure criterion which allows the comparison between different results. Under this aspect, the standardization of the measurement procedures still is necessary. http://sedici.unlp.edu.ar:80/handle/10915/7861 Revision New pharmaceutical forms as alternative for the treatment of tuberculosis to reduce cases of multi-drug resistance Latin American Journal of Pharmacy; vol. 28, no. 6 A tuberculose é uma doença negligenciada causada pelo Mycobacterium tuberculosis. São estimados dois milhões de óbitos e oito milhões de novos casos por ano, sendo 490.000 casos multi-droga resistentes. Fármacos anti-TB na forma de dose fixa combinada apresentam problemas relacionados à biodisponibilidade da rifampicina, que se relaciona com os casos de resistência. O investimento em tecnologia a fim de obter novas formas farmacêuticas tem se mostrado alternativa promissora para diminuir os casos de resistência e contribuir com a prevenção, controle e cura.; Tuberculosis is a neglected disease caused by Mycobacterium tuberculosis. Two million deaths and eight million new cases per year are estimated, with 490,000 cases multi-drug resistant. Anti-TB drugs as fixed-dose combination have problems inherent to the bioavailability of rifampicin, which is related to the cases of resistance. The investment in technology to achieve new pharmaceutical forms has shown promising alternative to reduce the cases of resistance and contribute to the prevention, control and cure. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7861 2009-01-01T00:00:00Z A tuberculose é uma doença negligenciada causada pelo Mycobacterium tuberculosis. São estimados dois milhões de óbitos e oito milhões de novos casos por ano, sendo 490.000 casos multi-droga resistentes. Fármacos anti-TB na forma de dose fixa combinada apresentam problemas relacionados à biodisponibilidade da rifampicina, que se relaciona com os casos de resistência. O investimento em tecnologia a fim de obter novas formas farmacêuticas tem se mostrado alternativa promissora para diminuir os casos de resistência e contribuir com a prevenção, controle e cura. Tuberculosis is a neglected disease caused by Mycobacterium tuberculosis. Two million deaths and eight million new cases per year are estimated, with 490,000 cases multi-drug resistant. Anti-TB drugs as fixed-dose combination have problems inherent to the bioavailability of rifampicin, which is related to the cases of resistance. The investment in technology to achieve new pharmaceutical forms has shown promising alternative to reduce the cases of resistance and contribute to the prevention, control and cure. http://sedici.unlp.edu.ar:80/handle/10915/7860 Comunicacion Topic antiinflammatory activity of extracts from Hydrocotyle bonariensis Lam. (Apiaceae)?. Latin American Journal of Pharmacy; vol. 28, no. 6 Hydrocotyle bonariensis Lam. (Apiaceae), "redondita de agua", "paragüita" o "tembladerilla", es una especie sudamericana empleada en medicina popular principalmente contra eritemas cutáneos. Los resultados obtenidos indican que tanto la infusión como el extracto metanólico de las partes aéreas inhiben significativamente el edema de oreja en ratón (inflamación local), con valores entre el 30 y 58%, respectivamente, validando su uso popular. No se observaron efectos antiinflamatorios por vía oral.; Hydrocotyle bonariensis Lam. (Apiaceae), ("redondita de agua", "paragüita" or "tembladerilla", is a South American species employed in popular medicine against cutaneous eritemas. The results indicate that both the infusion and the methanol extract of aerial parts significantly inhibited mouse ear edema (local swelling), with values between 30 and 58% respectively, confirming the popular use ot this species. No significant anti-inflammatory effects were observed by oral administration. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7860 2009-01-01T00:00:00Z Hydrocotyle bonariensis Lam. (Apiaceae), "redondita de agua", "paragüita" o "tembladerilla", es una especie sudamericana empleada en medicina popular principalmente contra eritemas cutáneos. Los resultados obtenidos indican que tanto la infusión como el extracto metanólico de las partes aéreas inhiben significativamente el edema de oreja en ratón (inflamación local), con valores entre el 30 y 58%, respectivamente, validando su uso popular. No se observaron efectos antiinflamatorios por vía oral. Hydrocotyle bonariensis Lam. (Apiaceae), ("redondita de agua", "paragüita" or "tembladerilla", is a South American species employed in popular medicine against cutaneous eritemas. The results indicate that both the infusion and the methanol extract of aerial parts significantly inhibited mouse ear edema (local swelling), with values between 30 and 58% respectively, confirming the popular use ot this species. No significant anti-inflammatory effects were observed by oral administration. http://sedici.unlp.edu.ar:80/handle/10915/7859 Comunicacion Development and study of the physicochemical stability of W/O/W and O/W/O multiple emulsions increased of chemical filters and shea butter Latin American Journal of Pharmacy; vol. 28, no. 6 O objetivo deste trabalho foi desenvolver e avaliar a estabilidade físico-química de emulsões múltiplas A/O/A e O/A/O acrescidas de filtros químicos e manteiga de karité. As formulações foram preparadas pelo método de duas etapas e permaneceram em observação durante uma semana para análise visual, sendo que a mais estável foi selecionada para prosseguimento dos estudos. A avaliação da estabilidade foi realizada em diferentes temperaturas (estufa, geladeira e temperatura ambiente) durante 30 dias, avaliando-se as características organolépticas, pH e viscosidade. Os resultados evidenciaram que a formulação mantida em temperatura ambiente e em geladeira apresentou maior estabilidade físico-química e menor variação de viscosidade no período analisado, sendo que a temperatura influenciou nos valores de viscosidade. Conclui-se que é possível formular emulsões múltiplas A/O/A estáveis com metoxicinamato de isoamila e manteiga de karité.; The aim of this work was to develope and evaluate the physical-chemistry stability of W/O/W and O/W/O multiple emulsions increased of chemical filters and shea butter. The formulations were prepared using the two-step procedure and remained in observation during one week for visual analysis, and the most steady was selected for continuation the studies. The stability evaluation was performed at different temperatures (oven, refrigerator and room temperature) over 30 days and its organoleptic characteristics, pH and viscosity were evaluated. The results evidenced that the formulation kept at room temperature and refrigerator presented greater physical-chemistry stability and minor variation of viscosity in the analyzed period, the temperature influencing in the viscosity values. It was concluded that is possible to formulate A/O/A multiple emulsions steady with isoamyl methoxycinnamate and shea butter. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7859 2009-01-01T00:00:00Z O objetivo deste trabalho foi desenvolver e avaliar a estabilidade físico-química de emulsões múltiplas A/O/A e O/A/O acrescidas de filtros químicos e manteiga de karité. As formulações foram preparadas pelo método de duas etapas e permaneceram em observação durante uma semana para análise visual, sendo que a mais estável foi selecionada para prosseguimento dos estudos. A avaliação da estabilidade foi realizada em diferentes temperaturas (estufa, geladeira e temperatura ambiente) durante 30 dias, avaliando-se as características organolépticas, pH e viscosidade. Os resultados evidenciaram que a formulação mantida em temperatura ambiente e em geladeira apresentou maior estabilidade físico-química e menor variação de viscosidade no período analisado, sendo que a temperatura influenciou nos valores de viscosidade. Conclui-se que é possível formular emulsões múltiplas A/O/A estáveis com metoxicinamato de isoamila e manteiga de karité. The aim of this work was to develope and evaluate the physical-chemistry stability of W/O/W and O/W/O multiple emulsions increased of chemical filters and shea butter. The formulations were prepared using the two-step procedure and remained in observation during one week for visual analysis, and the most steady was selected for continuation the studies. The stability evaluation was performed at different temperatures (oven, refrigerator and room temperature) over 30 days and its organoleptic characteristics, pH and viscosity were evaluated. The results evidenced that the formulation kept at room temperature and refrigerator presented greater physical-chemistry stability and minor variation of viscosity in the analyzed period, the temperature influencing in the viscosity values. It was concluded that is possible to formulate A/O/A multiple emulsions steady with isoamyl methoxycinnamate and shea butter. http://sedici.unlp.edu.ar:80/handle/10915/7858 Comunicacion Comparative analysis of capsules of sibutramine acquired in formal and informal market Latin American Journal of Pharmacy; vol. 28, no. 6 A sibutramina é um fármaco anorexígeno indicado para o tratamento da obesidade e redução de peso corpóreo, em conjunto com dieta e exercícios físicos. No Brasil, encontra-se comercialmente na forma farmacêutica de cápsulas de 10 mg e 15 mg. Medicamentos contendo este fármaco são adquiridos hoje no Brasil no mercado formal e informal. Portanto este trabalho tem como objetivo fazer análise comparativa de uniformidade de massa e conteúdo entre o medicamento de referência, genérico, similar, manipulado e o comercializado no mercado informal por espectrofotometria na região do ultravioleta. Conforme os resultados obtidos, em relação ao peso médio todas as amostras cumpriram as especificações, já no teste de uniformidade de conteúdo somente a amostra adquirida no mercado informal apresentou concentração de substância ativa fora das especificações farmacopêicas.; Sibutramine is an anorexigenic agent indicated for the treatment of obesity and body weight reduction, together with a food diet and physical exercises. In Brazil, it is found commercially in the pharmaceutical form of 10 and 15 mg capsules. Medication containing this agent can be purchased in Brazil nowadays in both the formal and informal market. Hence, the aim of this study is to do a comparative analysis of uniformity of mass and content between the reference, the generic, the similar, the homeopathic and the informally commercialised medicines, by using spectrophotometry in the ultraviolet region. According to the results obtained, as to the average weight all the samples have fulfilled the specifications; however, in the uniformity of content test only the sample acquired in the informal market presented irregular concentration of the active substance. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7858 2009-01-01T00:00:00Z A sibutramina é um fármaco anorexígeno indicado para o tratamento da obesidade e redução de peso corpóreo, em conjunto com dieta e exercícios físicos. No Brasil, encontra-se comercialmente na forma farmacêutica de cápsulas de 10 mg e 15 mg. Medicamentos contendo este fármaco são adquiridos hoje no Brasil no mercado formal e informal. Portanto este trabalho tem como objetivo fazer análise comparativa de uniformidade de massa e conteúdo entre o medicamento de referência, genérico, similar, manipulado e o comercializado no mercado informal por espectrofotometria na região do ultravioleta. Conforme os resultados obtidos, em relação ao peso médio todas as amostras cumpriram as especificações, já no teste de uniformidade de conteúdo somente a amostra adquirida no mercado informal apresentou concentração de substância ativa fora das especificações farmacopêicas. Sibutramine is an anorexigenic agent indicated for the treatment of obesity and body weight reduction, together with a food diet and physical exercises. In Brazil, it is found commercially in the pharmaceutical form of 10 and 15 mg capsules. Medication containing this agent can be purchased in Brazil nowadays in both the formal and informal market. Hence, the aim of this study is to do a comparative analysis of uniformity of mass and content between the reference, the generic, the similar, the homeopathic and the informally commercialised medicines, by using spectrophotometry in the ultraviolet region. According to the results obtained, as to the average weight all the samples have fulfilled the specifications; however, in the uniformity of content test only the sample acquired in the informal market presented irregular concentration of the active substance. http://sedici.unlp.edu.ar:80/handle/10915/7857 Comunicacion Latin American Journal of Pharmacy; vol. 28, no. 6 Diuretics are an attractive class of drugs for the treatment of various disorders and in combination with some cardiovascular drugs. In the present work, 2D and 3D quantitative structure-activity relationship studies have been conducted on a series of diuretics. Significant correlation coefficients (r2 = 0.81 and q2 = 0.65, r2 = 0.91 and q2 = 0.85) were obtained, indicating potential of the models generated for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contributions should be useful for the design of diuretics having improved potency. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7857 2009-01-01T00:00:00Z Diuretics are an attractive class of drugs for the treatment of various disorders and in combination with some cardiovascular drugs. In the present work, 2D and 3D quantitative structure-activity relationship studies have been conducted on a series of diuretics. Significant correlation coefficients (r2 = 0.81 and q2 = 0.65, r2 = 0.91 and q2 = 0.85) were obtained, indicating potential of the models generated for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contributions should be useful for the design of diuretics having improved potency. http://sedici.unlp.edu.ar:80/handle/10915/7856 Comunicacion Latin American Journal of Pharmacy; vol. 28, no. 6 In this study, calcium antagonistic activity of sixteen hexahydroquinoline derivatives have been elucidated in rat ileum and rat thorasic aorta. In the studies on isolated rat ileum, it has been observed that all compounds showed meaningfull activity. In rat thorasic aorta studies, compound 3a has been found more active than nicardipine. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7856 2009-01-01T00:00:00Z In this study, calcium antagonistic activity of sixteen hexahydroquinoline derivatives have been elucidated in rat ileum and rat thorasic aorta. In the studies on isolated rat ileum, it has been observed that all compounds showed meaningfull activity. In rat thorasic aorta studies, compound 3a has been found more active than nicardipine. http://sedici.unlp.edu.ar:80/handle/10915/7855 Comunicacion Essential oils composition of <i>Salvia lachnostachys</i> and <i>S. melissiflora</i> (Lamiaceae) Latin American Journal of Pharmacy; vol. 28, no. 6 Os óleos essenciais de Salvia lachnostachys (folhas e flores) e S. melissiflora (folhas), obtidos por hidrodestilação, foram analisados por CG e CG/EM. Os óleos foram caracterizados por um elevado teor de compostos alifáticos. Nos óleos de S. lachnostachys o componente majoritário foi o ácido dodecanóico (folhas 61,6%, flores 73,4%). No óleo das folhas de S. melissiflora os componentes principais foram ácido linoleico (29,3%), ácido hexadecanóico (11,3%) e óxido de cariofileno (9,6%). Este é o primeiro relato de estudo de óleos essenciais nestas duas espécies.; The essential oils isolated by hydrodistillation of Salvia lachnostachys Benth. (leaves and flowers) and S. melissiflora Benth. (leaves) were analyzed by capillary GC/MS. The oils were characterized by high content of aliphatic compounds. In the essential oils of S. lachnostachys the major component was dodecanoic acid (61.6% in leaves and 73.4% in flowers). In the essential oil of S. melissiflora the main components were linoleic and hexadecanoic acids (29.3% and 11.3%, respectively) and caryophyllene oxide (9.6%). This paper describes for the first time the composition of essential oils of S. lachnostachys and S. melissiflora. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7855 2009-01-01T00:00:00Z Os óleos essenciais de Salvia lachnostachys (folhas e flores) e S. melissiflora (folhas), obtidos por hidrodestilação, foram analisados por CG e CG/EM. Os óleos foram caracterizados por um elevado teor de compostos alifáticos. Nos óleos de S. lachnostachys o componente majoritário foi o ácido dodecanóico (folhas 61,6%, flores 73,4%). No óleo das folhas de S. melissiflora os componentes principais foram ácido linoleico (29,3%), ácido hexadecanóico (11,3%) e óxido de cariofileno (9,6%). Este é o primeiro relato de estudo de óleos essenciais nestas duas espécies. The essential oils isolated by hydrodistillation of Salvia lachnostachys Benth. (leaves and flowers) and S. melissiflora Benth. (leaves) were analyzed by capillary GC/MS. The oils were characterized by high content of aliphatic compounds. In the essential oils of S. lachnostachys the major component was dodecanoic acid (61.6% in leaves and 73.4% in flowers). In the essential oil of S. melissiflora the main components were linoleic and hexadecanoic acids (29.3% and 11.3%, respectively) and caryophyllene oxide (9.6%). This paper describes for the first time the composition of essential oils of S. lachnostachys and S. melissiflora. http://sedici.unlp.edu.ar:80/handle/10915/7854 Comunicacion Latin American Journal of Pharmacy; vol. 28, no. 6 The aim of the present study was to investigate the role of liver in progression of insulin resistance in relation to IGF-I levels in rats with acute hepatotoxicity, induced by carbon tetrachloride (CCl4) and acetaminophen. Wistar rats were divided into four equal groups of six rats each. Group-I (served as Control1) received olive oil, group-II received CCl4, group-III (served as control 2) received gum acacia and group-IV received acetaminophen. After 48 h of treatment, fasting blood samples were collected to determine biochemical parameters, and liver and pancreas in all groups were collected for histological evaluations. The levels of serum fasting glucose, AST, ALT, ALP, total bilirubin and insulin resistance were Significantly more in group II & IV when compared with their respective control groups. Fasting insulin and IGF-I levels in toxicant treated groups were shown significantly lower than in control groups. The liver sections of toxicant treated rats showed hydropic degeneration (ballooning) in centrilobular hepatocytes with single cell necrosis surrounded by neutrophils. The serum IGF-I level could be a useful marker for identifying subjects at risk of developing type-II diabetes mellitus and possible cardiovascular complications. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7854 2009-01-01T00:00:00Z The aim of the present study was to investigate the role of liver in progression of insulin resistance in relation to IGF-I levels in rats with acute hepatotoxicity, induced by carbon tetrachloride (CCl4) and acetaminophen. Wistar rats were divided into four equal groups of six rats each. Group-I (served as Control1) received olive oil, group-II received CCl4, group-III (served as control 2) received gum acacia and group-IV received acetaminophen. After 48 h of treatment, fasting blood samples were collected to determine biochemical parameters, and liver and pancreas in all groups were collected for histological evaluations. The levels of serum fasting glucose, AST, ALT, ALP, total bilirubin and insulin resistance were Significantly more in group II & IV when compared with their respective control groups. Fasting insulin and IGF-I levels in toxicant treated groups were shown significantly lower than in control groups. The liver sections of toxicant treated rats showed hydropic degeneration (ballooning) in centrilobular hepatocytes with single cell necrosis surrounded by neutrophils. The serum IGF-I level could be a useful marker for identifying subjects at risk of developing type-II diabetes mellitus and possible cardiovascular complications. http://sedici.unlp.edu.ar:80/handle/10915/7853 Articulo Calendula officinalis: Central depressive effect and subacute toxicity Latin American Journal of Pharmacy; vol. 28, no. 6 Flowers of Calendula officinalis L. (calendula) have been popularly used due to some attributed medicinal properties as wound healing, anti-inflammatory and sedative activites. The principal chemical compounds found in flowers are essential oils, salicilic acid, carotenoids, flavonoids, tannins and triterpenic saponins.Other medicinal plants that present flavonoids in his composition have also been used as ansiolitic and analgesic. In this work the activity of calendula was evaluated on the central nervous system, with models of sleep induced by barbiturates, rota rod and open field. Subacute toxicity was evaluated in rats in metabolic cages. Central depressive effect was observed, with decrease of the spontaneous movement. Hypoglycemic effect was observed but signs of subcute toxicity were not evidenced.; Flores da Calendula officinalis L. (calêndula) vêm sendo utilizadas popularmente como cicatrizante, antiinflamatório e sedativo, entre outras atividades. Os principais componentes químicos encontrados nas flores são óleos essenciais, ácido salicílico, carotenóides, flavonóides, taninos e saponinas triterpênicas. Atividades ansiolítica e analgésica foram relatadas em plantas que apresentam flavonóides em sua composição. Nesse trabalho a atividade do extrato etanólico das flores da calêndula sobre o sistema nervoso central foi avaliada por meio dos modelos do sono induzido por barbitúricos, do rota rod e do campo aberto. A toxicidade subaguda do extrato por via oral também foi testada em ratos por meio de gaiolas metabólicas. Observou-se efeito depressor central, com diminuição da movimentação espontânea. Observou- se efeito hipoglicemiante e não foram evidenciados sinais de toxicidade suaguda. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7853 2009-01-01T00:00:00Z Flowers of Calendula officinalis L. (calendula) have been popularly used due to some attributed medicinal properties as wound healing, anti-inflammatory and sedative activites. The principal chemical compounds found in flowers are essential oils, salicilic acid, carotenoids, flavonoids, tannins and triterpenic saponins.Other medicinal plants that present flavonoids in his composition have also been used as ansiolitic and analgesic. In this work the activity of calendula was evaluated on the central nervous system, with models of sleep induced by barbiturates, rota rod and open field. Subacute toxicity was evaluated in rats in metabolic cages. Central depressive effect was observed, with decrease of the spontaneous movement. Hypoglycemic effect was observed but signs of subcute toxicity were not evidenced. Flores da Calendula officinalis L. (calêndula) vêm sendo utilizadas popularmente como cicatrizante, antiinflamatório e sedativo, entre outras atividades. Os principais componentes químicos encontrados nas flores são óleos essenciais, ácido salicílico, carotenóides, flavonóides, taninos e saponinas triterpênicas. Atividades ansiolítica e analgésica foram relatadas em plantas que apresentam flavonóides em sua composição. Nesse trabalho a atividade do extrato etanólico das flores da calêndula sobre o sistema nervoso central foi avaliada por meio dos modelos do sono induzido por barbitúricos, do rota rod e do campo aberto. A toxicidade subaguda do extrato por via oral também foi testada em ratos por meio de gaiolas metabólicas. Observou-se efeito depressor central, com diminuição da movimentação espontânea. Observou- se efeito hipoglicemiante e não foram evidenciados sinais de toxicidade suaguda. http://sedici.unlp.edu.ar:80/handle/10915/7852 Articulo Quality evaluation of pantoprazole gastro-resistant compounded capsules Latin American Journal of Pharmacy; vol. 28, no. 6 O pantoprazol é um agente anti-úlcera inibidor da bomba de prótons. Doze lotes de cápsulas gastro-resistentes de pantoprazol sódico sesquiidratado, equivalente a 40 mg de pantoprazol, manipuladas por farmácias, foram avaliadas por ensaios de determinação de peso, uniformidade de conteúdo, desintegração, dissolução e doseamento. Lotes de cápsulas preenchidas com pellets industrializados cumpriram com as especificações para os ensaios, especialmente, gastro-resistência. Outros lotes, preparados por métodos alternativos para conferir gastro-resistência, apresentaram problemas na gastro-resistência, dissolução, doseamento e uniformidade de conteúdo. Lotes de cápsulas revestidas com acetoftalato de celulose, goma laca, formol e de cápsulas contendo grânulos preparados com acetoftalato de celulose não apresentaram gastro-resistência. Dos lotes preparados por métodos alternativos, somente aquele constituído por cápsulas revestidas e também, preenchidas com grânulos preparados com Eudragit® L100 na própria farmácia apresentou gastro-resistência adequada. Esta pesquisa revela a necessidade do setor magistral se adequar e cumprir com especificações para a manipulação de cápsulas gastro-resistentes.; Pantoprazole is an anti-ulcer proton pump inhibitor. Twelve lots of pantoprazole sodium sesquihydrate gastro-resistant capsules equivalent to 40 mg of pantoprazole compounded by pharmacies were evaluated by weight determination, content uniformity, disintegration, dissolution and assay. Capsule lots filled with pellets met gastro-resistance and other requirements. Other lots prepared by alternative methods to give gastro-resistance showed problems in the gastro-resistance, dissolution, assay and content uniformity. Capsule lots coated with cellulose acetophtalate, gum lacquer, formaldehyde and capsules lots filled with cellulose acetophtalate granules did not exhibit gastroresistance. Among lots compounded by alternative methods, only that constituted of capsules coated and also filled with granules prepared with Eudragit® L100 at the pharmacy, exhibited appropriate gastro-resistance. This research reveals the need of the pharmacies to adjust and meet specification criteria for compounding gastro-resistant capsules. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7852 2009-01-01T00:00:00Z O pantoprazol é um agente anti-úlcera inibidor da bomba de prótons. Doze lotes de cápsulas gastro-resistentes de pantoprazol sódico sesquiidratado, equivalente a 40 mg de pantoprazol, manipuladas por farmácias, foram avaliadas por ensaios de determinação de peso, uniformidade de conteúdo, desintegração, dissolução e doseamento. Lotes de cápsulas preenchidas com pellets industrializados cumpriram com as especificações para os ensaios, especialmente, gastro-resistência. Outros lotes, preparados por métodos alternativos para conferir gastro-resistência, apresentaram problemas na gastro-resistência, dissolução, doseamento e uniformidade de conteúdo. Lotes de cápsulas revestidas com acetoftalato de celulose, goma laca, formol e de cápsulas contendo grânulos preparados com acetoftalato de celulose não apresentaram gastro-resistência. Dos lotes preparados por métodos alternativos, somente aquele constituído por cápsulas revestidas e também, preenchidas com grânulos preparados com Eudragit® L100 na própria farmácia apresentou gastro-resistência adequada. Esta pesquisa revela a necessidade do setor magistral se adequar e cumprir com especificações para a manipulação de cápsulas gastro-resistentes. Pantoprazole is an anti-ulcer proton pump inhibitor. Twelve lots of pantoprazole sodium sesquihydrate gastro-resistant capsules equivalent to 40 mg of pantoprazole compounded by pharmacies were evaluated by weight determination, content uniformity, disintegration, dissolution and assay. Capsule lots filled with pellets met gastro-resistance and other requirements. Other lots prepared by alternative methods to give gastro-resistance showed problems in the gastro-resistance, dissolution, assay and content uniformity. Capsule lots coated with cellulose acetophtalate, gum lacquer, formaldehyde and capsules lots filled with cellulose acetophtalate granules did not exhibit gastroresistance. Among lots compounded by alternative methods, only that constituted of capsules coated and also filled with granules prepared with Eudragit® L100 at the pharmacy, exhibited appropriate gastro-resistance. This research reveals the need of the pharmacies to adjust and meet specification criteria for compounding gastro-resistant capsules. http://sedici.unlp.edu.ar:80/handle/10915/7851 Articulo Latin American Journal of Pharmacy; vol. 28, no. 6 This study evaluated the antimicrobial activity of the crude ethanol extract and fractions from Eugenia uniflora L. leaves against Pseudomonas aeruginosa. A total of 72 P. aeruginosa isolated from patients of three hospitals in Goiânia and 8 standard strains were selected to test antimicrobial activity. The bacteria susceptibility profile against 15 antimicrobial agents was determined using the disc diffusion method. The minimum inhibitory concentration of the crude ethanol extract and the ethyl acetate, chloroform and hexane fractions was determined. Most of the P. aeruginosa analyzed proved resistant to a number of antimicrobial substances and their sensitivity varied from 81.9% sensitivity to meropenem to 0.0% sensitivity to cefotaxim. All the P. aeruginosa were inhibited by the crude extract and by the ethyl acetate fraction. Only 11.25% of the bacteria analyzed were inhibited by the chloroform fraction (8.75 mg/mL MIC). The hexane fraction presented no activity. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7851 2009-01-01T00:00:00Z This study evaluated the antimicrobial activity of the crude ethanol extract and fractions from Eugenia uniflora L. leaves against Pseudomonas aeruginosa. A total of 72 P. aeruginosa isolated from patients of three hospitals in Goiânia and 8 standard strains were selected to test antimicrobial activity. The bacteria susceptibility profile against 15 antimicrobial agents was determined using the disc diffusion method. The minimum inhibitory concentration of the crude ethanol extract and the ethyl acetate, chloroform and hexane fractions was determined. Most of the P. aeruginosa analyzed proved resistant to a number of antimicrobial substances and their sensitivity varied from 81.9% sensitivity to meropenem to 0.0% sensitivity to cefotaxim. All the P. aeruginosa were inhibited by the crude extract and by the ethyl acetate fraction. Only 11.25% of the bacteria analyzed were inhibited by the chloroform fraction (8.75 mg/mL MIC). The hexane fraction presented no activity. http://sedici.unlp.edu.ar:80/handle/10915/7850 Articulo Formulation additives on formation of films isolated from ethylcellulose. Physicochemical and morphological studies Latin American Journal of Pharmacy; vol. 28, no. 6 Neste trabalho foram produzidos filmes isolados de etilcelulose em base aquosa (Surelease®) contendo os aditivos α-GOS (α-glucoligossacarídeo) e/ou Tween® 80, os quais foram obtidos sobre placas de Teflon® pelo método de casting process. Os filmes foram caracterizados pelas seguintes análises: Calorimetria diferencial de varredura (DSC), termogravimetria (TG), espectroscopia na região do infravermelho (FTIR-ATR) e microscopia eletrônica de varredura (MEV). As análises de DSC e TG evidenciaram que os aditivos de formulação não influenciaram na estabilidade térmica dos filmes de Surelease®. Pelas análises das micrografias obtidas por MEV, os filmes apresentaram características morfológicas homogê- neas e ausência de separação de fase. Isto também foi verificado através dos espectros de FTIR-ATR os quais confirmaram haver somente mistura física entre os componentes dos filmes.; In this work were developed free films from Surelease®, additives α-GOS (alfa-glucooligosaccharide) and/or Tween® 80 in aqueous solution. It was obtained by Teflon plates “casting” process. The free films were characterized by thermal analysis (DSC and TGA), infrared spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM). DSC and TG analysis showed that the additives do not influenced in the thermal stability of Surelease® films. SEM analysis observed homogeneous morphological characteristics and phase detachment absence. FTIR-ATR spectra were used to confirm the physical mixture between the components of films. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7850 2009-01-01T00:00:00Z Neste trabalho foram produzidos filmes isolados de etilcelulose em base aquosa (Surelease®) contendo os aditivos α-GOS (α-glucoligossacarídeo) e/ou Tween® 80, os quais foram obtidos sobre placas de Teflon® pelo método de casting process. Os filmes foram caracterizados pelas seguintes análises: Calorimetria diferencial de varredura (DSC), termogravimetria (TG), espectroscopia na região do infravermelho (FTIR-ATR) e microscopia eletrônica de varredura (MEV). As análises de DSC e TG evidenciaram que os aditivos de formulação não influenciaram na estabilidade térmica dos filmes de Surelease®. Pelas análises das micrografias obtidas por MEV, os filmes apresentaram características morfológicas homogê- neas e ausência de separação de fase. Isto também foi verificado através dos espectros de FTIR-ATR os quais confirmaram haver somente mistura física entre os componentes dos filmes. In this work were developed free films from Surelease®, additives α-GOS (alfa-glucooligosaccharide) and/or Tween® 80 in aqueous solution. It was obtained by Teflon plates “casting” process. The free films were characterized by thermal analysis (DSC and TGA), infrared spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM). DSC and TG analysis showed that the additives do not influenced in the thermal stability of Surelease® films. SEM analysis observed homogeneous morphological characteristics and phase detachment absence. FTIR-ATR spectra were used to confirm the physical mixture between the components of films. http://sedici.unlp.edu.ar:80/handle/10915/7849 Articulo NTPDase activity of lymphocytes in contact dermatitis before and after treatment with nanostructured dexamethasone Latin American Journal of Pharmacy; vol. 28, no. 6 Foi estudada a hidrólise de nucleotídeos da adenina pela NTPDase em linfócitos de ratos Wistar com dermatite induzida por sulfato de níquel, antes e após tratamento com dexametasona livre e nanoestruturada. Os dois tipos de tratamento também foram avaliados por análise histopatológica e morfométrica. A atividade enzimática média do grupo com dermatite de contato foi significativamente maior em relação ao grupo controle (P<0,001). A hidrólise do ATP e do ADP nos grupos tratado com dexametasona livre e nanoestruturada foi significativamente maior em relação ao grupo controle (P < 0,001). Não se observou aumento estatisticamente significativo na hidrólise de ADP e ATP, entre os grupos tratados com dexametasona nanoestruturada ou livre. Houve um maior grau de atrofia da pele no grupo tratado com dexametasona nanoestruturada sugerindo ter este, efeito imunossupressor maior. O aumento na atividade da NTPDase, provavelmente ocorreu por mecanismos compensatórios, devido a inibição da proliferação dos linfócitos pela dexametasona, indicando alteração pela resposta imune.; The hydrolysis of adenine nucleotides by NTPDase was studied in lymphocytes of Wistar rats with experimental nickel-sulphate induced dermatitis, before and after treatment with free and nanostructured dexamethasone. Both treatments were also evaluated by histopathological and morphometric analysis. The mean enzymatic activity of the contact dermatitis group was significantly greater compared to the control group (P < 0.001). ATP and ADP hydrolysis were significantly greater in the free and nanostructured treatment groups when compared to the control group (P < 0.001). ADP and ATP hydrolysis were not statistically significant different between the two treatment groups. The group treated with nanostructured dexamethasone showed greater skin atrophy, suggesting that this treatment has a greater immunosuppressant effect. The increase in NTPDase activity probably occurred through compensatory mechanisms, due to inhibition of lymphocyte proliferation by dexmethasone, indicating an alteration in the immune response. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7849 2009-01-01T00:00:00Z Foi estudada a hidrólise de nucleotídeos da adenina pela NTPDase em linfócitos de ratos Wistar com dermatite induzida por sulfato de níquel, antes e após tratamento com dexametasona livre e nanoestruturada. Os dois tipos de tratamento também foram avaliados por análise histopatológica e morfométrica. A atividade enzimática média do grupo com dermatite de contato foi significativamente maior em relação ao grupo controle (P<0,001). A hidrólise do ATP e do ADP nos grupos tratado com dexametasona livre e nanoestruturada foi significativamente maior em relação ao grupo controle (P < 0,001). Não se observou aumento estatisticamente significativo na hidrólise de ADP e ATP, entre os grupos tratados com dexametasona nanoestruturada ou livre. Houve um maior grau de atrofia da pele no grupo tratado com dexametasona nanoestruturada sugerindo ter este, efeito imunossupressor maior. O aumento na atividade da NTPDase, provavelmente ocorreu por mecanismos compensatórios, devido a inibição da proliferação dos linfócitos pela dexametasona, indicando alteração pela resposta imune. The hydrolysis of adenine nucleotides by NTPDase was studied in lymphocytes of Wistar rats with experimental nickel-sulphate induced dermatitis, before and after treatment with free and nanostructured dexamethasone. Both treatments were also evaluated by histopathological and morphometric analysis. The mean enzymatic activity of the contact dermatitis group was significantly greater compared to the control group (P < 0.001). ATP and ADP hydrolysis were significantly greater in the free and nanostructured treatment groups when compared to the control group (P < 0.001). ADP and ATP hydrolysis were not statistically significant different between the two treatment groups. The group treated with nanostructured dexamethasone showed greater skin atrophy, suggesting that this treatment has a greater immunosuppressant effect. The increase in NTPDase activity probably occurred through compensatory mechanisms, due to inhibition of lymphocyte proliferation by dexmethasone, indicating an alteration in the immune response. http://sedici.unlp.edu.ar:80/handle/10915/7848 Articulo From theory to practice: Experience of implementation of pharmaceutical care in Minas Gerais, Brazil Latin American Journal of Pharmacy; vol. 28, no. 6 A atenção farmacêutica é uma prática centrada no paciente que tem como objetivo primário prevenir e resolver problemas relacionados ao uso de medicamentos. As discussões acerca dessa prática vêm ganhando o centro das discussões entre pesquisadores, formuladores de políticas e profissionais farmacêuticos. Entretanto, o que vem acontecendo é que o discurso está sobressaindo em relação à prática. O presente trabalho buscou, a partir das experiências de farmacêuticos, descrever o processo de implantação de um serviço de atenção farmacêutica em farmácia comunitária. Utilizou método qualitativo e as técnicas da observação participante e entrevistas semi-estruturadas. Os resultados revelam quatro etapas vividas pelos farmacêuticos durante o processo e desvela os aspectos fundamentais da implantação da atenção farmacêutica em farmácia comunitária fornecendo uma trilha que poderá ser contemplada por profissionais farmacêuticos interessados em seguir esse caminho profissional.; Pharmaceutical care is a patient-centered practice whose goal is to prevent and resolve drug therapy problems. Even though pharmaceutical care was accepted by the profession of pharmacy as its new professional mandate, for the most part, there is much more discourse than practice as it relates to taking care of real patients. This study aimed to describe the process of implementation of pharmaceutical care in a community pharmacy from the perspectives of pharmacists. It was used qualitative methodology and the methods of participant observation and semi-structured interviews. The results unravel four stages experienced by pharmacists during the implementation process. This study unveil fundamental aspects of the implementation of pharmaceutical care in community pharmacy offering a trail that can be take into account by pharmacists who are willing to follow this professional path. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7848 2009-01-01T00:00:00Z A atenção farmacêutica é uma prática centrada no paciente que tem como objetivo primário prevenir e resolver problemas relacionados ao uso de medicamentos. As discussões acerca dessa prática vêm ganhando o centro das discussões entre pesquisadores, formuladores de políticas e profissionais farmacêuticos. Entretanto, o que vem acontecendo é que o discurso está sobressaindo em relação à prática. O presente trabalho buscou, a partir das experiências de farmacêuticos, descrever o processo de implantação de um serviço de atenção farmacêutica em farmácia comunitária. Utilizou método qualitativo e as técnicas da observação participante e entrevistas semi-estruturadas. Os resultados revelam quatro etapas vividas pelos farmacêuticos durante o processo e desvela os aspectos fundamentais da implantação da atenção farmacêutica em farmácia comunitária fornecendo uma trilha que poderá ser contemplada por profissionais farmacêuticos interessados em seguir esse caminho profissional. Pharmaceutical care is a patient-centered practice whose goal is to prevent and resolve drug therapy problems. Even though pharmaceutical care was accepted by the profession of pharmacy as its new professional mandate, for the most part, there is much more discourse than practice as it relates to taking care of real patients. This study aimed to describe the process of implementation of pharmaceutical care in a community pharmacy from the perspectives of pharmacists. It was used qualitative methodology and the methods of participant observation and semi-structured interviews. The results unravel four stages experienced by pharmacists during the implementation process. This study unveil fundamental aspects of the implementation of pharmaceutical care in community pharmacy offering a trail that can be take into account by pharmacists who are willing to follow this professional path. http://sedici.unlp.edu.ar:80/handle/10915/7847 Articulo Latin American Journal of Pharmacy; vol. 28, no. 6 Ethanol extract and fractions from aerial parts of Eclipta alba (L.) Hassk (Asteraceae) were screened for the antibacterial and antifungal activities against different species of human pathogenic bacterial ATCC, antibiotic-resistant clinical isolates and strains of the dermatophyte Trichophyton rubrum (wild and mutant for TruMDR2 gene) using a microdilution method. Demethylwedelolactone/wedelolactone (DWL/WL) and only wedelolactone (WL), both in a high homogeneity degree, were efficient to inhibit the ATCC strains of Staphylococus aureus (Minimal Inhibitory Concentration MIC = 75 μg/mL), Staphylococcus epidemidis (MIC = 125 μg/mL) and Escherichia coli (MIC = 125 μg/mL) as well as antibiotic-resistant clinical isolates of Enterococcus spp (MIC = 250 μg/mL) and S. aureus (MIC = 125 μg/mL). Ethanol extract was more effective than the purified fractions against Trichophyton rubrum strains (MIC = 125 μg/mL), suggesting that anti-fungal activity is not only related to demethylwedelolactone and wedelolactone, but also to a synergistic action between these coumestans and other compounds found in that extract. Thus, this work suggests that E. alba possesses a significant antimicrobial activity, including that against multi-drug resistant microorganisms, which could be of relevance for the treatment of infectious diseases. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7847 2009-01-01T00:00:00Z Ethanol extract and fractions from aerial parts of Eclipta alba (L.) Hassk (Asteraceae) were screened for the antibacterial and antifungal activities against different species of human pathogenic bacterial ATCC, antibiotic-resistant clinical isolates and strains of the dermatophyte Trichophyton rubrum (wild and mutant for TruMDR2 gene) using a microdilution method. Demethylwedelolactone/wedelolactone (DWL/WL) and only wedelolactone (WL), both in a high homogeneity degree, were efficient to inhibit the ATCC strains of Staphylococus aureus (Minimal Inhibitory Concentration MIC = 75 μg/mL), Staphylococcus epidemidis (MIC = 125 μg/mL) and Escherichia coli (MIC = 125 μg/mL) as well as antibiotic-resistant clinical isolates of Enterococcus spp (MIC = 250 μg/mL) and S. aureus (MIC = 125 μg/mL). Ethanol extract was more effective than the purified fractions against Trichophyton rubrum strains (MIC = 125 μg/mL), suggesting that anti-fungal activity is not only related to demethylwedelolactone and wedelolactone, but also to a synergistic action between these coumestans and other compounds found in that extract. Thus, this work suggests that E. alba possesses a significant antimicrobial activity, including that against multi-drug resistant microorganisms, which could be of relevance for the treatment of infectious diseases. http://sedici.unlp.edu.ar:80/handle/10915/7846 Articulo Latin American Journal of Pharmacy; vol. 28, no. 6 Calea clematidea and Calea uniflora are native shrubs found in the southern Brazil. In previous study, C. zacatechichi extracts showed psychopharmacologic properties. The aim of this paper is to investigate the effect of these two plants on CNS and genotoxic effects in rats. Methanolic extracts of C. clematidea and C. uniflora showed apparent efficacy in decreasing the number of entries in closed arms, but no species tested affected the number of entries or time spent in the open arms in the elevated plusmaze test. C. clematideae and C. uniflora did not change the number of crossings and rearings performed in the open field task. Both extracts did not induce DNA damage in brain tissue from treated animals, assessed by comet assay. The results suggest C. clematidea and C. uniflora do not induce anxiolytic and genotoxic effects, nor do they alter locomotor activity in rats. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7846 2009-01-01T00:00:00Z Calea clematidea and Calea uniflora are native shrubs found in the southern Brazil. In previous study, C. zacatechichi extracts showed psychopharmacologic properties. The aim of this paper is to investigate the effect of these two plants on CNS and genotoxic effects in rats. Methanolic extracts of C. clematidea and C. uniflora showed apparent efficacy in decreasing the number of entries in closed arms, but no species tested affected the number of entries or time spent in the open arms in the elevated plusmaze test. C. clematideae and C. uniflora did not change the number of crossings and rearings performed in the open field task. Both extracts did not induce DNA damage in brain tissue from treated animals, assessed by comet assay. The results suggest C. clematidea and C. uniflora do not induce anxiolytic and genotoxic effects, nor do they alter locomotor activity in rats. http://sedici.unlp.edu.ar:80/handle/10915/7845 Articulo Relation between CYP2C19 phenotype and amitriptyline demethylation metabolic ratios in healthy volunteers Latin American Journal of Pharmacy; vol. 28, no. 6 A enzima CYP2C19 é a principal responsável pela metabolização da amitriptilina, com a formação de nortriptilina. Após fenotipagem com omeprazol em um grupo de 38 voluntários saudáveis, 5 voluntários com variados fenótipos (1 metabolizador lento, 1 metabolizador ultra-rápido e 3 metabolizadores rápidos) receberam uma dose oral única de amitriptilina e os níveis plasmáticos de amitriptilina e de seu metabólito principal nortriptilina foram monitorados. As razões de desmetilação de amitriptilina foram marcantemente diferentes entre indivíduos com diferentes fenótipos e correlacionadas com as razões metabólicas obtidas com omeprazol. As concentrações plasmáticas de amitriptilina e nortriptilina obtidas após uma dose oral de amitriptilina podem ser utilizadas para predição da exposição ao fármaco e para o ajuste precoce da posologia.; CYP2C19 is the main responsible enzyme by amitriptyline metabolism, leading to the formation of nortriptyline. After phenotyping with omeprazole in a group of 38 healthy volunteers, 5 volunteers with different phenotypes (1 poor metabolizer, 1 ultra-extensive metabolizer and 3 extensive metabolizer) received a single oral dose of amitriptyline and the plasma levels of both amitriptyline and its main metabolite nortriptyline were monitored. Amitriptyline demethylation ratios were markedly different among individuals with different phenotypes and were correlated with omeprazole hydroxilation ratios. Plasma levels of amitriptyline and nortriptyline obtained after a single oral dose of amitriptyline can be used to prediction of drug exposure and to the early adjustment of the dosage regimen. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7845 2009-01-01T00:00:00Z A enzima CYP2C19 é a principal responsável pela metabolização da amitriptilina, com a formação de nortriptilina. Após fenotipagem com omeprazol em um grupo de 38 voluntários saudáveis, 5 voluntários com variados fenótipos (1 metabolizador lento, 1 metabolizador ultra-rápido e 3 metabolizadores rápidos) receberam uma dose oral única de amitriptilina e os níveis plasmáticos de amitriptilina e de seu metabólito principal nortriptilina foram monitorados. As razões de desmetilação de amitriptilina foram marcantemente diferentes entre indivíduos com diferentes fenótipos e correlacionadas com as razões metabólicas obtidas com omeprazol. As concentrações plasmáticas de amitriptilina e nortriptilina obtidas após uma dose oral de amitriptilina podem ser utilizadas para predição da exposição ao fármaco e para o ajuste precoce da posologia. CYP2C19 is the main responsible enzyme by amitriptyline metabolism, leading to the formation of nortriptyline. After phenotyping with omeprazole in a group of 38 healthy volunteers, 5 volunteers with different phenotypes (1 poor metabolizer, 1 ultra-extensive metabolizer and 3 extensive metabolizer) received a single oral dose of amitriptyline and the plasma levels of both amitriptyline and its main metabolite nortriptyline were monitored. Amitriptyline demethylation ratios were markedly different among individuals with different phenotypes and were correlated with omeprazole hydroxilation ratios. Plasma levels of amitriptyline and nortriptyline obtained after a single oral dose of amitriptyline can be used to prediction of drug exposure and to the early adjustment of the dosage regimen. http://sedici.unlp.edu.ar:80/handle/10915/7844 Articulo Average bioequivalence taking into account the gender of subjects Latin American Journal of Pharmacy; vol. 28, no. 6 Los mayores obstáculos para la toma de decisiones en bioequivalencia promedio están referidos al tamaño de la variabilidad residual. Se ha visto que en ella incide mucho las características de los individuos reclutados para el ensayo. El presente trabajo propone una metodología que estudia la varianza residual según el género de los voluntarios y construye intervalos de confianza para el cociente de medias Test / Referencia (T/R), de los parámetros de biodisponibilidad, tanto en hombres como en mujeres. Asimismo se analizan las varianzas totales producidas por los medicamentos T y R, a los efectos de complementar la toma de decisiones. Las anteriores pautas fueron aplicadas a 3 estudios de bioequivalencia llevados a cabo con fármacos sustratos de la isoenzima CYP3A4 (itraconazol, alprazolam, claritromicina), algunos de los cuales son también sustratos del transportador de eflujo P-glicoproteína. Las mujeres presentaron menor exposición a los fármacos sustratos de CYP3A4 que los hombres. Los medicamentos T y R, conteniendo tales fármacos, mostraron biodisponibilidades relativas dependientes del sexo de los voluntarios, principalmente a causa de probables diferencias de disolución, originadas por la diferente fisiología del tracto digestivo que presentan hombres y mujeres. Como conclusión de este trabajo se entiende que la toma de decisiones en bioequivalencia debería tener en cuenta los resultados obtenidos en cada género, para apoyar tanto que T y R sean bioequivalentes como que sean bioinequivalentes.; Conclusions on average bioequivalence are mainly impaired because of the study variability. Very often individual characteristics play a major role in determining the size of the trial residual variance. The ANOVA residual variance and the point estimate for the test / reference (T/R) ratio of bioavailability means were analyzed in this paper taking into account the gender of subjects. Total variances issued by each drug product, in each group of volunteers, were also considered in this new proposal. The method was applied to data collected in 3 previous bioequivalence studies carried out with CYP3A4 isoenzyme substrates (itraconazole, alprazolam and clarithromycin), being some of them also P-glycoprotein substrates. Women showed lower plasma drug exposure than men. Test and reference products containing such CYP3A4 substrates displayed relative bioavailabilities mainly dependent on the gender gastrointestinal physiology. Difference in drug dissolution in the gastrointestinal tract seems to be the main reason for some test-reference bioinequivalence trends. As a conclusion, drug product performances in men and women should be considered for bioequivalence decision making. Thu, 01 Jan 2009 00:00:00 GMT http://sedici.unlp.edu.ar:80/handle/10915/7844 2009-01-01T00:00:00Z Los mayores obstáculos para la toma de decisiones en bioequivalencia promedio están referidos al tamaño de la variabilidad residual. Se ha visto que en ella incide mucho las características de los individuos reclutados para el ensayo. El presente trabajo propone una metodología que estudia la varianza residual según el género de los voluntarios y construye intervalos de confianza para el cociente de medias Test / Referencia (T/R), de los parámetros de biodisponibilidad, tanto en hombres como en mujeres. Asimismo se analizan las varianzas totales producidas por los medicamentos T y R, a los efectos de complementar la toma de decisiones. Las anteriores pautas fueron aplicadas a 3 estudios de bioequivalencia llevados a cabo con fármacos sustratos de la isoenzima CYP3A4 (itraconazol, alprazolam, claritromicina), algunos de los cuales son también sustratos del transportador de eflujo P-glicoproteína. Las mujeres presentaron menor exposición a los fármacos sustratos de CYP3A4 que los hombres. Los medicamentos T y R, conteniendo tales fármacos, mostraron biodisponibilidades relativas dependientes del sexo de los voluntarios, principalmente a causa de probables diferencias de disolución, originadas por la diferente fisiología del tracto digestivo que presentan hombres y mujeres. Como conclusión de este trabajo se entiende que la toma de decisiones en bioequivalencia debería tener en cuenta los resultados obtenidos en cada género, para apoyar tanto que T y R sean bioequivalentes como que sean bioinequivalentes. Conclusions on average bioequivalence are mainly impaired because of the study variability. Very often individual characteristics play a major role in determining the size of the trial residual variance. The ANOVA residual variance and the point estimate for the test / reference (T/R) ratio of bioavailability means were analyzed in this paper taking into account the gender of subjects. Total variances issued by each drug product, in each group of volunteers, were also considered in this new proposal. The method was applied to data collected in 3 previous bioequivalence studies carried out with CYP3A4 isoenzyme substrates (itraconazole, alprazolam and clarithromycin), being some of them also P-glycoprotein substrates. Women showed lower plasma drug exposure than men. Test and reference products containing such CYP3A4 substrates displayed relative bioavailabilities mainly dependent on the gender gastrointestinal physiology. Difference in drug dissolution in the gastrointestinal tract seems to be the main reason for some test-reference bioinequivalence trends. As a conclusion, drug product performances in men and women should be considered for bioequivalence decision making.