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Vol. 6. Núm. G.
Tratamiento de las hiperlipemias en pacientes con riesgo cardiovascular elevado
Páginas 52G-62G (Septiembre 2006)
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Vol. 6. Núm. G.
Tratamiento de las hiperlipemias en pacientes con riesgo cardiovascular elevado
Páginas 52G-62G (Septiembre 2006)
Tratamiento de las hiperlipemias en pacientes con riesgo cardiovascular elevado
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Doble inhibición del colesterol: papel de la regulación intestinal y hepática
Dual Cholesterol Inhibition: Roles of Intestinal and Hepatic Regulation
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...
Emilio Ros??
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eros@clinic.ub.es

Correspondencia: Dr. E. Ros. Unidad de Lípidos. Servicio de Endocrinología y Nutrición. Hospital Clínic. Villarroel, 170. 08036 Barcelona. España.
Unidad de Lípidos. Servicio de Endocrinología y Nutrición. IDIBAPS. Hospital Clínic. Barcelona. España
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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

Many patients at a high cardiovascular disease risk do not reach current treatment goals when given statins as monotherapy. A therapeutic approach that complements cholesterol synthesis inhibition is desirable in these patients; it is currently available: inhibition of intestinal cholesterol absorption, the second pathway for cholesterol homeostasis in the body. Regulation of intestinal cholesterol absorption is a critical therapeutic target because the efficiency of this process determines both fecal cholesterol loss and the amount of cholesterol delivered to the liver via chylomicron remnants. The mass of intestinal cholesterol reaching the liver exerts important regulatory effects: it suppresses, to a variable extent, both cholesterol synthesis and LDL receptor expression. Generally, this means that there are only small increases in blood cholesterol level in response to increased intestinal cholesterol load. Ezetimibe, a selective cholesterol absorption inhibitor, reversibly suppresses the activity of the intestinal transport protein NPC1L1. In addition to inhibiting cholesterol absorption, ezetimibe also inhibits net phytosterol absorption. Because it is not metabolized via the cytochrome P450 pathway, ezetimibe has little potential for pharmacokinetic interactions. The administration of 10 mg/day as monotherapy reduces cholesterol absorption by close to 50%, and this is associated with an average 18% decrease in LDL-cholesterol level. The hypocholesterolemic effects of ezetimibe are additive to those of statins, which is a reason why this drug combination is currently the treatment of choice for attaining LDL-cholesterol goals in most high-risk patients.

Key words:
Cholesterol
Phytosterols
Intestinal absorption
Hypolipidemic drugs
Ezetimibe
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