Lecithin: cholesterol acyltransferase activity in familial hypercholesterolemia treated with simvastatin and simvastatin plus low-dose colestipol.
(1991) The Journal of Clinical Pharmacology — Vol. 31, n° 6, p. 537-542 (1991)
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- 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 HDL2-HDL3 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 HDL2-C concentration. This original design allowed to define the most appropriate individual cholesterol-lowering drug dosage in FH patients.
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Desager, J.-P., Horsmans, Y., & Harvengt, C. (1991). Lecithin: cholesterol acyltransferase activity in familial hypercholesterolemia treated with simvastatin and simvastatin plus low-dose colestipol. The Journal of Clinical Pharmacology, 31(6), 537-542. https://hdl.handle.net/2078.5/211832 (Original work published 1991)