Interações medicamentaosas: definições e mecanismos / Drug interactions: definitions and mechanisms

Com mudanças na expectativa de vida, comorbidades edisponibilidade de novos fármacos, aumentou a ocorrênciade interações medicamentosas por mecanismos farmacocinéticose farmacodinâmicos. Para a biotransformação dosmedicamentos, os organismos desenvolveram sistemas enzimáticoscapazes de metabolizar e excretar esses produtos.Os polimorfismos genéticos dessas enzimas condicionamsua eficiência em metabolizar determinados medicamentos.A conjugação com moléculas solúveis em água, adicionadasao medicamento, facilitam sua excreção. Os transportadoresdesempenham importante papel no influxo, efluxo e na excreçãode medicamentos através dos sistemas biliar e urinário.O tratamento de doenças cardiovasculares frequentementeenvolve uso de múltiplos fármacos, principalmente nos pacientesidosos e portadores de comorbidades. Nesse sentido, éimportante o conhecimento dessas interações medicamentosas,frequentemente responsáveis pelos insucessos terapêuticos epela ocorrência de efeitos adversos...

With changes in life expectancy, co-morbidities and theavailability of new drugs, the occurrence of drug interactionsby pharmacokinetic and pharmacodynamic mechanisms hasincreased. For the bio-transformations of medications theorganisms have developed enzymatic systems able to metabolizeand excrete these products. The genetic polymorphisms ofthese enzymes affect their efficiency in metabolizing certaindrugs. The combination with water-soluble molecules addedto the medication facilitates the excretion. Transporters playan important role in the inflow, outflow and the excretion ofmedications through the biliary and urinary systems. Thetreatment of cardiovascular diseases often involves the useof multiple drugs especially in elderly patients and patientswith co-morbidities. In this sense, it is very important theknowledge about these drugs interactions which are oftenresponsible for the therapeutic failure and for the occurrenceof adverse effects...

Conversión de sandimmune a neoral en pacientes trasplantados renales que reciben ciclosporina-ketoconazol / Conversion of sandimmune to neoral in patients with renal transplantation treated with cyclosporine-ketoconazol

Patients and methods: Thirty four patients with more than one year after the transplantation, with stable renal function and receiving triple immunosuppression were studied. Conventional cyclosporine was changed to the microemulsion form maintaining the same daily dose. Drug serum levels, serum creatinine and blood pressure were measured within two to eight months after the conversion. Doses of microemulsion cyclosporine were adjusted to achieve serum levels of 150 ñ 40 ng/ml. Results: Microemulsion cyclosporine induced a slight initial increase in blood cyclosporine levels. Afterwards, levels were more stable than with conventional cyclosporine (165-185 and 145-210 ng/ml respectively) and the dispersion of values were lower (standard deviations of 70 and 100 ng/ml respectively). Twenty three patients did not require dose adjustments, in four it was reduced and in five it was increased. There were no changes in serum creatinine or blood pressure after the conversion. Conslusion: More stable serum levels without adverse reactions were obtained with microemulsion cyclosporine. Doses of cyclos porine need not to be changed during the conversion

Pruebas de sensibilidad in vitro para levaduras: evaluación de un micrométodo / In vitro susceptibility tests for yeasts: evaluation of a micromethod

Se evaluó un micrométodo para la realización de pruebas de sensibilidad de levaduras frente a antifúngicos, basado en el macrométodo en medio líquido estandarizado por el National Committee for Clinical Laboratory Standards (NCCLS) Subcommittee on Antifungal Susceptibility Testing. En este trabajo se compararon ambos métodos utilizando 6 cepas de referencia de diferente sensibilidad a los siguientes antifúngicos, anfotericina B (AMB), flucitosina (5FC), fluconazol (FCZ), itraconazol (ITZ), ketoconazol (KTZ) y miconazol (MCZ). Se observaron variaciones de sólo 1 ó 2 diluciones entre los resultados de las concentraciones inhibitorias mínimas (CIM) obtenidas con las dos técnicas. Asimismo, se compararon las lecturas visuales de CIM por micrométodo con las mediciones turbidimétricas del crecimiento en distintas concentraciones de antifúngicos frente a 47 aislamientos de Candida albicans. Existió una correlación significativa (p<0.001) entre CIM visual y la inhibición del 80 por ciento de crecimiento determinada por turbidimetría con AMB, 5FC, FCZ, ITZ y MCZ; en cambio no hubo correlación alguna para KTZ (p=1.00)

Estudio de establidad y compatibilidad del ketoconazol / Stability and compatibility studies of Ketoconazole

Se estudia la degradación del ketoconazol en condiciones aceleradas de degradación y su compatibilidad química en los excipientes más comunes empleados en la formulación de formas farmacéuticas tópicas. Se obtiene como resultado que el principio activo es compatible con los excipientes considerados a excepción del polietilenglicol 400, así como que es resistente a la degradación en las condiciones expuestas

Pharmacokinetic interactions of ketoconazole with rifampicin in human volunteers

The interaction of ketoconazole [antifungal agent] and rifampicin [antitubeculosis agent] was studied in the serum of ten healty human volunteers [male], having age between 20 to 30 years and weight from 54 to 72 kg. The blood samples were collected after administrating rifampicin alone and currently with ketoconazole at different time intervals. The serum was separated and stored [-20°C]. Reverse phase HPLC was used as analytical tool to determine the serum concentrations of rifampicin. The influence of ketoconazole on the pharmacokinetic parameters [AUC, Cmax, t1/2, Ke, Ka and tmax] of rifampicin was assessed, when both the drugs were administered simultaneously. It was observed that AUC and Cmax got decreased highly significantly [p<0.001], while t ' reduced and Ke increased significantly [p<0.05]. Statistically significant increase in the values of Ka and tmax was also observed

El caso de infecciosas: micosis sistematicas severas y su tratamiento con derivados imidazolicos / The infectious case: severe systemic mycoses and its treatment using imidazolic derivates

Se describen tres casos severos de paracoccidiodomicosis e histoplasmosis en pacientes jovenes (7 a 21 anos) quienes recibieron como tratamiento unico compuestos imidazolicos (ketoconazol 200 mg. itraconazol 100 mg/dia); estos fueron administrados por via oral por periodos variables (14-24 meses). Los pacientes empezaron a mejorar desde los tres primeros meses de terapia, aumentando dicha mejoria con el transcurso del tiempo. Durante la terapia no se detectaron alteraciones en las pruebas hepaticas o hematologicas, como tampoco efectos secundarios significativos. Los controles post-tratamiento han sido llevados a cabo por mas de dos anos sin que se hayan encontrado signos de reactivacion de la micosis. Los resultados clinicos, serologicos y radiologicos obtenidos en los pacientes bajo estudio, permiten aceptar que estos compuestos imidazolicos son una alternativa valiosa para el manejo de casos graves de histoplasmosis y de paracocciodiodomicosis.