Probucol

Abstract

Probucol is a potent synthetic lipophilic antioxidant which was developed in the 1960s for the plastics and rubber industry by Dow Chemicals Co. In a series of screening assays it was found to lower plasma cholesterol in animals. This effect was reproduced in man and probucol was first licensed for treatment of hypercholesterolemia in Europe in 1976 (Portugal and Spain) and in the United States and Canada in 1978. Although the drug was well tolerated, effective in heterozygous familial hypercholesterolemia (FH), and able to induce xanthoma regression, probucol was initially received with little enthusiasm because it lowered plasma high-density lipoproteins (HDL), an effect considered invariably unfavorable at the time, and had a long plasma half-life. In recent years, however, the interest in probucol was rekindled for several reasons (Davignon 1991a): the HDL-lowering effect was not shown to be deleterious, combination therapy with resins proved to be highly effective at lowering low-density lipoproteins (LDL) and it could induce xanthoma regression in homozygous FH and retard progression of atherosclerosis in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an effect ascribed to its antioxidant properties, and further studies uncovered new and rather unexpected potential benefits. The aim of this review is to outline what is known about probucol that is of practical importance for the treatment of hyperlipidemia and atherosclerosis, with an emphasis on antioxidant properties and new observations. For further details, the reader is referred to previous reviews (Murphy 1977; Heel et al. 1978; Strandberg et al. 1988; Buckley et al. 1989).