Effect of probucol treatment on lipoprotein cholesterol and drug levels in blood and lipoproteins in familial hypercholesterolemia.
Twelve patients with mild and 3 with severe hypercholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL3 cholesterol was reduced significantly throughout the period (P less than 0.001), HDL2 cholesterol showed a significant decrease only at the 4th week of treatment (P less than 0.001), and returned to basal levels at the 8th and 12th treatment weeks. Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period. In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third. Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.
Fellin
R
R
Gasparotto
A
A
Valerio
G
G
Baiocchi
M R
MR
Padrini
R
R
Lamon
S
S
Vitale
E
E
Baggio
G
G
Crepaldi
G
G
D000328:Adult; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D008075:Lipoproteins, HDL / Q000097:blood; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D010636:Phenols / Q000627:therapeutic use*; D011341:Probucol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010636:Phenols; D011341:Probucol