MICROSOMAL-ENZYME INDUCERS RAISE PLASMA HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVELS IN HEALTHY CONTROL SUBJECTS BUT NOT IN PATIENTS WITH PRIMARY HYPOALPHALIPOPROTEINEMIA
G. Franceschini et al., MICROSOMAL-ENZYME INDUCERS RAISE PLASMA HIGH-DENSITY-LIPOPROTEIN CHOLESTEROL LEVELS IN HEALTHY CONTROL SUBJECTS BUT NOT IN PATIENTS WITH PRIMARY HYPOALPHALIPOPROTEINEMIA, Clinical pharmacology and therapeutics, 57(4), 1995, pp. 434-440
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.