Farmacología de los azoles

Abstract

Los azoles presentan características farmacocinéticas diferenciadas, con una absorción oral completa de voriconazol, menor de fluconazol y menos importante y que aumenta con alimentos en el caso de posaconazol e itraconazol. Todos presentan una distribución tisular elevada, que se manifiesta por concentraciones plasmáticas muy reducidas, especialmente en el caso de posaconazol e itraconazol. Estos dos últimos fármacos presentan una fracción libre reducida al circular en plasma unidos a proteínas en proporción elevada. La eliminación es en todos los casos a través de metabolismo con intervención de diversas isoenzimas CYP450, a las que son capaces de inhibir, lo que condiciona una farmacocinética no lineal y un elevado riesgo de interacciones con otros fármacos. Es posible que el parámetro que mejor defina la eficacia sea el AUIC con un valor óptimo de 20. Si esta circunstancia se concreta, debe valorarse el punto de corte para la sensibilidad puesto que algunos de estos fármacos pueden tener dificultades para alcanzar este valor.Farmacología, Posaconazol, Itraconazol, Fluconazol, Voriconazol Pharmacology of azolesAzole antifungals have different pharmacokinetic characteristics: complete oral absorption for Voriconazole, and to a lesser extent for fluconazole. The absorption of posaconazole and itraconazole increases with food intake. All of them have high tissue distribution with low plasma concentrations, especially low in the case of posaconazole and itraconazole. Posaconazole and itraconazole have high plasmatic protein binding and consequently both have a very low free fraction. Elimination of azole antifungals is through a metabolic pathway with CYP450 isoenzymes, and has a non linear pharmacokinetics with a high risk of interation with other drugs since azoles have the ability of CYP450 isoenzymes inhibition. Possibly the parameter that defines more precisely their efficacy is AUIC with an optimum value near 20, although cut-off values must be defined since some azoles may have difficulty to reach this value.Pharmacology, Posaconazole, Itraconazole, Fluconazole, Voriconazole Los azoles forman una familia heterogénea de fár-macos que comparten la presencia de un anillo azólico central y con ello el mecanismo de acción antifúngico, que consiste en la inhibición de la síntesis del ergosterol. Al mismo tiempo los cuatro azoles de interés en el tratamiento de las infecciones sistémicas: fluconazol, itraconazol, voriconazol y posaconazol, presentan diferencias importantes en su estructura, con similitud entre ellos. Estas diferencias en la estructura generan comportamienDirección para correspondencia: Dr. José Ramón Azanza Servicio de Farmacología Clínica Clínica Universitaria de Navarra Avda. Pío XII s/n 31008 -Pamplona Tel.: (+34) 948 296 695 Fax: (+34) 948 296 500 E-mail: jrazanza@unav.es ©2007 Revista Iberoamericana de Micología Apdo. 699, E-48080 Bilbao (Spain) 1130-1406/01/10.00 tos farmacocinéticos distintos que tienen repercusiones notables en el manejo práctico de estos fármacos, a los que se hará refer...

A Transcriptomics Approach To Unveiling the Mechanisms of In Vitro Evolution towards Fluconazole Resistance of a Candida glabrata Clinical Isolate

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