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Lecithin: Cholesterol Acyltransferase Activity in Familial Hypercholesterolemia Treated with Simvastatin and Simvastatin Plus Low‐Dose Colestipol
Author(s) -
Desager J. P.,
Horsmans Y.,
Harvengt C.
Publication year - 1991
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1991.tb03734.x
Subject(s) - simvastatin , sterol o acyltransferase , familial hypercholesterolemia , chemistry , cholesterol , endocrinology , lecithin , medicine , lecithin—cholesterol acyltransferase , regimen , apolipoprotein b , pharmacology , lipoprotein , biochemistry
In 19 patients with heterozygous familial hypercholesterolemia (FH), the effects of simvastatin (S) 20 mg/d, 40 mg/d, and 40 mg/d plus low‐dose colestipol (10 g/d) on plasma lipids, plasma lipoproteins, and plasma lecithin: cholesterol acyltransferase (LCAT) activity were investigated after an original dose‐range escalation/descalation design. The drug regimen was changed every 8 weeks. A significant reduction in total cholesterol and LDL‐cholesterol was observed, reaching 39% and 54% for the drug combination (week 28), and total apoprotein B and LDL‐apoprotein B were reduced by 39% and 50%, respectively. Triglycerides were significantly lowered by S alone (up to 29% with 40 mg/d). HDL‐cholesterol increased during therapy but the cholesterol content in HDL 2 ‐HDL 3 fractions (isolated by ultracentrifugation) did not change significantly during the different steps. The ratio LDL‐C/HDL‐C fell by 57% at week 28. Plasma LCAT activity expressed as FER was significantly enhanced by S alone (+33%), and a further increase on drug combination regimen (+58%) was observed. This effect could be considered as a consequence of the increased fractional clearance of LDL‐C. It tended to be sustained during the descalation part of the study. Biochemical adverse effects were scarce and transient in conclusion, the combination therapy increased the plasma LCAT/FER activity without a preferential enhancement in HDL 2 ‐C concentration. This original design allowed to define the most appropriate individual cholesterol‐lowering drug dosage in FH patients.