Mechanisms
Adding bezafibrate to long-term probucol therapy can trigger severe HDL and apolipoprotein A-I deficiency (Eur J Clin Pharmacol 1995)
Original title: High-density lipoprotein and apolipoprotein A-I deficiency induced by combination therapy with probucol and bezafibrate
Hypercholesterolaemic patients already on long-term probucol (mean 865 days) received add-on slow-release bezafibrate at 200 or 400 mg per day, with lipid profiles assessed over 12 months. Combination therapy significantly lowered total cholesterol, triglycerides, VLDL fractions, lipoprotein(a) and LCAT activity while raising HDL cholesterol, apolipoprotein A-I and apolipoprotein A-II overall, but five patients developed drastic HDL cholesterol reductions of 46.2%, 59.3% and 61.6% at 3, 6 and 12 months that reversed one month after stopping bezafibrate. In these HDL-deficient patients, serum probucol concentration was higher (56.2 versus 26.5 micrograms per mL) while CETP mass was significantly lower (2.08 versus 2.87 mg per L) than in patients without HDL deficiency, implicating probucol-CETP interactions in the reaction.
Original abstract
The effects of the administration of slow-release bezafibrate to hypercholesterolaemic patients who were already receiving long-term probucol treatment (mean 865 days, 500-1000 mg.day-1) were investigated. Bezafibrate was administered at either 200 mg.day-1 (13 males, 13 females, mean age 55.2 years) or 400 mg.day-1 (11 males, 14 females, mean age 57.2 years), and blood was taken at 0, 3, 6 and 12 months after the beginning of combination therapy. Overall, serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein (VLDL)-TC, high-density lipoprotein (HDL)-TG, VLDL-TG, VLDL-phospholipid (PL), lipoprotein (a) [Lp(a)], apolipoprotein (apo) C-III, apo E levels and LCAT activity decreased significantly with this combination therapy, while HDL cholesterol (C), HDL3-C, HDL-PL, apo A-I and apo A-II levels significantly increased, as assessed by analysis of variance (ANOVA). Five patients (one receiving 200 mg.day-1, four receiving 400 mg.day-1 bezafibrate) showed drastic reductions in HDL-C (HDL-C levels were reduced by a mean of 46.2%, 59.3% and 61.6% at 3, 6 and 12 months, respectively) after beginning combination therapy. These HDL-C reductions were maintained for the 1 year of combination therapy, but then returned to pre-combination treatment levels 1 month after discontinuation of bezafibrate. Serum probucol concentrations and cholesteryl ester transfer protein (CETP) mass were assayed at 6 months, and the probucol concentration was higher in the HDL-deficient group (56.2 vs 26.5 micrograms/ml). In contrast, CETP mass was significantly lower in HDL-deficient patients than in non-HDL-deficient patients (2.08 vs 2.87 mg.1-1)(ABSTRACT TRUNCATED AT 250 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.