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INTERACCIONES BILATERALES ENTRE CICLOSPORINA A Y TRATAMIENTOS HIPOLIPEMIANTES

(especial para SIIC © Derechos reservados)
La ciclosporina A tiene un índice terapéutico estrecho en receptores de trasplante de órganos sólidos, por lo cual es importante tener en cuenta todas las potenciales interacciones farmacocinéticas cuando se la administra simultáneamente con agentes que reducen los niveles de los lípidos en la sangre.
Autor:
Anders Asberg
Columnista Experto de SIIC

Institución:
Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo

Artículos publicados por Anders Asberg
Recepción del artículo
5 de Julio, 2005 		Aprobación
13 de Julio, 2005
Primera edición
20 de Febrero, 2006 		Segunda edición, ampliada y corregida
7 de Junio, 2021

INTERACCIONES BILATERALES ENTRE CICLOSPORINA A Y TRATAMIENTOS HIPOLIPEMIANTES

Resumen
En comparación con la población general, la dislipidemia es más frecuente en receptores de trasplantes de órganos sólidos, debido principalmente al tratamiento con drogas inmunosupresoras (como ciclosporina A [CsA] y esteroides). En estos pacientes, los fármacos hipolipemiantes se comenzaron a utilizar ampliamente, en especial los inhibidores de la enzima HMG-CoA reductasa (estatinas). Tanto la CsA como la mayoría de las estatinas son sustratos para la enzima CYP3A4, por lo que pueden producirse interacciones bilaterales entre ambos agentes farmacológicos. Sin embargo, los resultados de diversos estudios muestran que las estatinas no inducen un incremento clínicamente relevante en la exposición sistémica a la CsA. Por otro lado, el tratamiento con CsA provoca un aumento de varias veces en la exposición sistémica de todas las estatinas. No es probable que el mecanismo de esta interacción se deba a la inhibición del metabolismo de la CYP3A4, pero se sospecha que la CsA interfiere con el transporte de las estatinas en el organismo. Otros agentes hipolipemiantes, como los derivados del ácido fíbrico, los aceites de pescado y los que provocan el secuestro de sales biliares no interactúan con la farmacocinética de la CsA, pero existen informes que indican que tanto el probucol como el orlistat reducen la biodisponibilidad de la CsA a un nivel importante desde el punto de vista clínico.

Palabras clave
Ciclosporina A, estatinas, interacción farmacocinética, dislipidemia, colesterol


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THE BILATERAL INTERACTIONS BETWEEN CYCLOSPORINE A AND LIPID-LOWERING THERAPIES

Abstract
Dyslipidemia is more frequent in solid organ transplant recipients as compared to the general population, primarily due to the treatment with immunosuppressive drugs (i.e. cyclosporine A (CsA) and steroids). Lipid-lowering drugs have become widely used in this population, especially HMG-CoA reductase inhibitors (statins). CsA as well as most statins are substrates for CYP3A4 and a bilateral pharmacokinetic interaction between these drugs may occur. However, results from several studies show that statins do not induce clinically relevant increase in systemic exposure of CsA. On the other hand CsA treatment leads to several-fold higher systemic exposure of all statins. The mechanism for this interaction is not likely to be due to inhibition of CYP3A4 metabolism, but CsA is rather believed to interfere with statin-transport in the body. Other lipid-lowering drugs, such as fibric acid derivates, bile acid sequestrants and fish oils do not interact with CsA pharmacokinetics, but there are reports indicating that both probucol and orlistat reduce CsA bioavailability to a clinically relevant extent.

Key words
Cyclosporine A, statins, pharmacokinetic interaction, dyslipidemia, cholesterol


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Especialidades
Principal: Farmacología, Trasplantes
Relacionadas: Cardiología, Diagnóstico por Laboratorio, Inmunología, Medicina Farmacéutica, Medicina Interna



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