MICROSOMAL-ENZYME INDUCERS RAISE PLASMA HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVELS IN HEALTHY CONTROL SUBJECTS BUT NOT IN PATIENTS WITH PRIMARY HYPOALPHALIPOPROTEINEMIA

In this study we compared the ability of phenytoin, a microsomal enzym e inducer, to raise plasma high-density lipoprotein (HDL) levels in no rmolipidemic subjects and patients with primary hypoalphalipoproteinem ia. In healthy control subjects, phenytoin caused a dose-dependent inc rease of plasma HDL, HDL(2), and HDL(3) cholesterol levels, up to 40% to 50%. Minor changes were recorded in the plasma concentrations of ap olipoprotein (apo) A-I and apo A-II; the plasma level of the cholester yl ester transfer protein (CETP) decreased by 42%. In contrast, none o f the patients with hypoalphalipoproteinemia had changes in plasma HDL , HDL(2), or HDL(3) cholesterol, apo A-I, apo A-II, or CETP levels. Th ese findings indicate that microsomal enzyme inducers are unsuitable t o increase plasma HDL levels in highrisk patients with primary hypoalp halipoproteinemia, and they disclose a new mechanism, that is, decreas ed CETP-mediated transfer of cholesterol out of HDL, for the HDL-raisi ng effect of microsomal enzyme inducers in healthy individuals.