Figure 12 Structures of key compounds leading to the discovery of ezetimibe.

Figure 13 Structures of key probucol metabolites.

be taken at any time of day or night. Ezetimibe has no effect on the major drug-metabolizing enzymes and consequently its potential to cause drug-drug interactions is negligible. The molecular target for ezetimibe is the Niemann-Pick C1-Like1 protein that mediates cholesterol absorption within the brush-border membranes of intestinal enterocytes.74 This discovery should facilitate the search for new-generation cholesterol absorption inhibitors. Ezetimibe 10 was approved in 2002 in the US as monotherapy, and in 2004 as a fixed combination with simvastatin, known as Vytorin.

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