The pharmacology of cilostazol

Cilostazol (6‐[4‐(1‐cyclohexyl‐1H‐tetrazol‐5‐yl)butoxy]‐3,4‐dihydro‐2(1H)‐quinolinone; OPC‐13013) is a 2‐oxo‐quinoline derivative with antithrombotic, vasodilator, antimitogenic and cardiotonic properties. The compound is a potent inhibitor of phosphodiesterase (PDE) 3A, the isoform of PDE 3 in the cardiovascular system (IC50: 0.2 µm). In addition, there is inhibition of adenosine uptake, eventually resulting in changes in cAMP levels, dependent on the type of adenosine receptors (A1 or A2). Cilostazol inhibits platelet aggregation and has considerable antithrombotic effects in vivo. The compound relaxes vascular smooth muscle and inhibits mitogenesis and migration of vascular smooth muscle cells. In the heart, cilostazol causes positive inotropic and chronotropic effects. Most, if not all, of these actions are cAMP‐mediated, including the modification of cAMP‐controlled gene expression. Cilostazol decreases levels of serum triglycerides and causes some increase in HDL‐cholesterol levels. The compound has a number of additional effects which might contribute to its overall clinical efficacy. Cilostazol undergoes intensive and finally complete hepatic metabolism via the cytochrome P450 systems. This might result in some drug interaction, i.e. with erythromycin and omeprazole. The half‐life is approximately 10 h, resulting in about 2‐fold accumulation of the drug during repeated administration.