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 antiatheroscl erotic effect may result from the removal of oxidized cholesterol on the su rface of low-density lipoprotein (LDL). To investigate whether probucol tra nsfers 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 - mas s spectrometry, we identified cholesteryl-6-(2,6-di-tertiary butylphenol-4) -thioether (CT) in the urine samples from patients with hypercholesterolaem ia but not from healthy controls. This result suggests that probucol is hyd rolysed to form 4-mercapto-2,6-di-tertiary butylphenol (MBP) which conjugat es with cholesterol-5 alpha,6 alpha-epoxide, oxidized cholesterol, resultin g in the formation of CT in vivo. In addition to its hypolipidaemic and ant ioxidant actions, probucol may act to prevent atherosclerosis by increasing the urinary excretion of oxidized cholesterol.