High-density lipoprotein and apolipoprotein A-I deficiency induced by combination therapy with probucol and bezafibrate.
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)
Saku
K
K
Department of Internal Medicine, Fukuoka University School of Medicine, Japan.
Zhang
B
B
Jimi
S
S
Bai
H
H
Hirata
K
K
Sasaki
N
N
Liu
R
R
Arakawa
K
K
D000328:Adult; D000368:Aged; D001053:Apolipoproteins / Q000097:blood* / Q000187:drug effects*; D001629:Bezafibrate / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000627:therapeutic use*; D013997:Time Factors
D001053:Apolipoproteins; D004338:Drug Combinations; D008055:Lipids; D008075:Lipoproteins, HDL; D011341:Probucol; D001629:Bezafibrate