Pharmacokinetic Analysis of Antiplatelet Effect of Cilostazol and its Application to Drug Dosage Regime

Modeling Based on Reversible Inhibition of Phosphodiesterase in the Platelet

Abstract

Cilostazol is an antithrombotic drug expected to be useful in the treatment of chronic arterial occlusive diseases. Cilostazol is a potent inhibitor of human platelet aggregation and selectively inhibits human platelet cyclic adenosine monophosphate phosphodiesterase type III. In this paper, we describe a pharmacokinetic-pharmacodynamic model for ascertaining the antiplatelet effect of cilostazol considering the reversible inhibition of phosphodiesterase in the platelet. All data used for analysis were obtained from the literature. The estimation of average inhibition of phosphodiesterase was 59.7% following an oral administration with usual dose. A significant linear relationship between the calculated inhibitory effects on phosphodiesterase and on collagen-induced platelet aggregation was obtained (p< 0.05). Based on this finding, a new method was developed. for predicting inhibitory effects on the collagen-induced platelet aggregation following oral administration of cilostazol. This method is useful for planning a rational dosage regimen of cilostazol and for predicting the duration of antiplatelet activity after discontinuance of the drug.