Low Density Lipoprotein Cholesterol Lowering Agents Synthetic Antioxidants

The synthetic antioxidant probucol 11 was identified in the early 1960s as a modest lipid-lowering agent. Probucol lowers plasma LDLc in both animals and humans, but it also profoundly reduces HDLc. In clinical testing, probucol lowers LDLc by up to 20% but can lower HDLc by as much as 20-30%. The precise mechanism by which probucol lowers LDLc and HDLc is unknown; however, probucol is known to prevent the oxidation of LDLc both in vitro and in vivo. Probucol has shown favorable benefits in reducing restenosis in patients, but its effects on atherosclerosis have been variable. Probucol undergoes extensive metabolism and oxidative degradation75 to produce a variety of potentially toxic metabolites, including the spiroquinone 32 and the fe-quinone 33 (Figure 13), that have been implicated in causing QTc prolongation and fatal arrhythmia.76 Probucol 11 was approved in the US in the early 1980s, but, because of these safety concerns, it was voluntarily withdrawn from the US market in 1995, although it is still prescribed in certain parts of the world.

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