High-density lipoprotein and apolipoprotein A-I deficiency induced by combination therapy with probucol and bezafibrate

✍ Scribed by K. Saku; B. Zhang; S. Jimi; H. Bai; K. Hirata; N. Sasaki; R. Liu; K. Arakawa

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 776 KB
• Volume: 48-48
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00198300

✦ Synopsis

The effects of the administration of slowrelease 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 tug'day 1 (13 males, 13 females, mean age 55.2 years) or 400 rag-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 rag day-l 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 gg/ml). In contrast, CETP mass was significantly lower in HDL-deficient patients than in non-HDL-Part of this work was presented at the XIth International Symposium on Drugs Affecting Lipid Metabolism (DALM),