Effect of an inhibitor of 3-hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10-levels in patients with familial hypercholesterolemia.

We studied the effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum levels of lipoproteins and ubiquinone-10-in seven heterozygous patients with familial hypercholesterolemia. ML-236B was given at doses of 30 to 60 mg per day for 24 weeks. Serum cholesterol decreased from 390 +/- 9 to 303 +/- 8 mg per deciliter (101 +/- 0.2 to 7.88 +/- 0.2 mmol per liter, mean +/- S.E.M.; p less than 0.001) and serum triglyceride decreased from 137 +/- 18 to 87 +/- 9 mg per deciliter (1.55 +/- 0.20 to 0.98 +/- 0.01 mmol per liter; p less than 0.05). Intermediate-density-lipoprotein (DL) cholesterol, IDL triglyceride, low-density-lipoprotein (LDL) cholesterol, and LDL triglyceride decreased significantly (p less than 0.01, P less than 0.001, and P less than 0.001, respectively). However, there were no significant changes in very-low-density-lipoprotein (VLDL) cholesterol and triglyceride or high-density-lipoprotein (HDL) cholesterol. Serum ubiquinone-10 levels did not change, and LDL levels of ubiquinone-10 decreased by 50 per cent, from 0.39 +/- 0.07 to 0.20 +/- 0.01 microgram per milliliter (P less than 0.05). No adverse effects were observed. We conclude that ML-236B is effective in lowering serum cholesterol without lowering serum ubiquinone-10 in heterozygous patients with familial hypercholesterolemia.