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Journal of Lipid Research, Vol. 24, 588-595, May 1983
Copyright © 1983 by Lipid Research, Inc.

The hypolipidemic action of probucol: a study of its effects on high and low density lipoproteins

Ragheb F. Atmeh , Jennifer M. Stewart , David E. Boag , Christopher J. Packard , A. Ross Lorimer , and James Shepherd

University Departments of Biochemistry and Medical Cardiology, Royal Infirmary, Glasgow G4 OSF, United Kingdom

This study examines the effects of probucol (1 g/day) on the plasma concentration, composition, and metabolism of low and high density lipoproteins (LDL and HDL) in eleven hyperlipidemic subjects, (seven Type II and four Type IV). The drug lowered plasma cholesterol in the Type II patients by 11% (P < 0.02) without affecting triglyceride. Both LDL and HDL cholesterol levels fell by 6% and 26%, respectively. The small reduction in the former was not associated with a change in the composition of the lipoprotein nor with a measurable alteration in the level of circulating apoLDL. Kinetic studies revealed that probucol had no consistent effect on either the synthesis or catabolism of apoLDL. However, probucol did exert a potent influence on HDL, lowering the level of this lipoprotein in both the Type II and Type IV patients despite the fact that total plasma cholesterol in the latter group was unchanged by treatment. The fall in HDL mass largely affected the HDL₃ subfraction; HDL₂, which was initially low in our subjects, did not show a consistent response to therapy. Not all of the constituents in HDL were equally affected by the drug. Specifically, the fall in total plasma apoA levels (which derived from significant reductions in the rates of synthesis of apoproteins A-I and A-II) was less than that of HDL cholesterol. Direct measurement of the composition of the lipoprotein confirmed that during therapy it carried less cholesterol per unit protein. The significance of these observations in relation to the prophylaxis of ischemic heart disease is not yet clear, but it seems prudent at present to use probucol selectively in subjects who show a substantial hypocholesterolemic response that derives primarily from a reduction in circulating LDL.—Atmeh, R. F., J. M. Stewart, D. E. Boag, C. J. Packard, A. R. Lorimer, and J. Shepherd. The hypolipidemic action of probucol: a study of its effects on high and low density lipoproteins.

Supplementary key words HDL₂ • HDL₃ • fractional clearance rate • apoA-I • apoA-II • apoLDL

Submitted on February 24, 1982
Revised on January 3, 1983

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