The effect of probucol on oxidized cholesterol disposition in hyperlipidaemic patients.

Probucol is a cholesterol-lowering and antioxidant drug that has been shown to inhibit or delay the progression of atherosclerosis. This antiatherosclerotic effect may result from the removal of oxidized cholesterol on the surface of low-density lipoprotein (LDL). To investigate whether probucol transfers oxidized cholesterol from LDL to urine, urine samples were obtained from five patients with hypercholesterolaemia treated with 500-mg probucol orally daily and from five healthy controls. Using gas chromatography-mass spectrometry, we identified cholesteryl-6-(2,6-di-tertiary butylphenol-4)-thioether (CT) in the urine samples from patients with hypercholesterolaemia but not from healthy controls. This result suggests that probucol is hydrolysed to form 4-mercapto-2,6-di-tertiary butylphenol (MBP) which conjugates with cholesterol-5 alpha, 6 alpha-epoxide, oxidized cholesterol, resulting in the formation of CT in vivo. In addition to its hypolipidaemic and antioxidant actions, probucol may act to prevent atherosclerosis by increasing the urinary excretion of oxidized cholesterol.