Cilostazol, also sold as Pletal, is a drug used to prevent platelet aggregation, specifically treating symptoms of intermittent claudication caused by peripheral artery disease as well as preventing strokes. Cilostazol is ingested orally, and it enters the liver, where it is metabolized in the endoplasmic reticulum by cytochrome P450 3A4 into 4-hydroxycilostazol, and by cytochrome P450 2C19 and 3A5 into 4-cis-hydroxycilostazol. Each of these metabolites is further metabolized, 4-hydroxycilostazol into 3,4-dehydrocilostazol and 4-cis-hydroxycilostazol into 4'-trans-hydroxycilostazol respectively. These two metabolites are the active metabolites, and they both act to inhibit the action of cAMP-specific 3',5'-cyclic phosphodiesterase 4D in platelets. With this enzyme inhibited, it is unable to metabolize cAMP into AMP, which leads to a buildup of cAMP in the blood. cAMP in turn is known to prevent aggregation of platelets, by inhibiting their adhesion to collagen, as well as decreasing the amount of calcium within the cytosol, preventing granule release, which then prevents activation of other platelets.

Cilostazol Pathway References