En pacientes con alto riesgo cardiovascular, la inhibición aislada de la síntesis de colesterol con estatinas no siempre consigue los objetivos terapéuticos, por lo que es deseable un método complementario para reducir el colesterol. Éste es la inhibición de la absorción intestinal, la segunda vía en la homeostasis del colesterol en el organismo. La regulación de la absorción intestinal del colesterol es una importante diana terapéutica, porque la eficiencia de este proceso determina tanto la excreción fecal como la cantidad que llega al hígado con los remanentes de quilomicrones. Tras su llegada al hígado, el colesterol de origen intestinal ejerce efectos reguladores importantes: inhibición variable de la síntesis de colesterol y expresión de receptores para las lipoproteínas de baja densidad (LDL). Esto se traduce generalmente en aumentos discretos de la colesterolemia en respuesta a una sobrecarga de colesterol en el intestino. La ezetimiba, un inhibidor selectivo de la absorción del colesterol, inactiva de forma reversible la acción de la proteína transportadora intestinal NPC1L1. Además de inhibir la absorción del colesterol, la ezetimiba reduce también la absorción de fitosteroles. Puesto que no se metaboliza por la vía del citocromo P450, la enzetimiba no presenta interacciones farmacocinéticas. La administración de 10 mg/día en monoterapia reduce un 50% la absorción de colesterol, lo cual se asocia con un descenso medio del cLDL de un 18%. El efecto hipocolesterolemiante de la ezetimiba es sinérgico con el de las estatinas, lo cual hace que esta combinación terapéutica sea actualmente de elección para lograr los objetivos de cLDL en la mayoría de pacientes con alto riesgo.
Palabras clave
Colesterol
Fitosteroles
Absorción intestinal
Fármacos hipolipemiantes
Ezetimiba
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