EFFECTS OF KETOCONAZOLE ON PLASMA-LIPIDS AND LIPOPROTEIN(A) IN FAMILIAL HYPERCHOLESTEROLEMIA, COMPARED WITH SIMVASTATIN

Background: Ketoconazole is an imidazole derivative that is active as a broad-spectrum antifungal agent. It is also an inhibitor of choleste rol production both in vivo and in vitro. Methods: We compared the eff ect of low-dose ketoconazole (200 mg/day) or simvastatin (20-40 mg/day ) on lipids, lipoproteins and lipoprotein(a) [Lp(a)] in 10 patients wi th familial hypercholesterolaemia. Results: Ketoconazole reduced serum total cholesterol and low-density lipoprotein (LDL)-cholesterol by 7. 6 and 9.7%, respectively. Simvastatin was more effective, the respecti ve changes being -34.4 and -40.6%. Serum triglycerides and high-densit y lipoprotein (HDL) were unchanged by ketoconazole therapy, whereas si mvastatin decreased triglyceride levels by 33.8% and increased HDL-cho lesterol levels by 8.7%. Median Lp(a) levels tended to increase during simvastatin and to decrease during ketoconazole therapy. However, due to the wide range of baseline concentrations of Lp(a), these changes were not significant. Conclusions: Ketoconazole has some hypocholester olaemic potential. but the effect of simvastatin is much more pronounc ed. The increase in Lp(a) during simvastatin therapy has been reported earlier, whereas ketoconazole does not exhibit an effect on the level of Lp(a). (C) 1997 Elsevier Science B.V.