Key result
A single 100 mg dose of cilostazol in healthy volunteers resulted in a mean peak concentration of 775 ng/ml, a 31.14% maximal reduction in platelet aggregation, and a 13.49% maximal increase in heart rate.
Why the study?
What is the pharmacokinetic-pharmacodynamic relationship of a single 100 mg oral dose of cilostazol on platelet aggregation and cardiovascular effects in healthy humans?
What is the pharmacokinetic-pharmacodynamic relationship of a single 100 mg oral dose of cilostazol on platelet aggregation and cardiovascular effects in healthy humans?
A 2-compartment pharmacokinetic-pharmacodynamic model successfully describes the time course of cilostazol's antiplatelet and vasodilatory effects following a single oral dose.
Single-dose PK-PD data in healthy volunteers extend modeling; leaves open translation to patients with vascular disease.
OBJECTIVE: Cilostazol is an antiplatelet agent with vasodilating properties. It has been used to treat patients with peripheral ischemia, such as intermittent claudication. We used a pharmacokinetic-pharmacodynamic model to analyze the relation between the plasma concentration of cilostazol, the inhibitory effect of the drug on platelet aggregation, and the cardiovascular effects of the drug on healthy humans. METHODS: A single oral dose of 100 mg cilostazol was administered to 20 healthy volunteers. Serial blood sampling and pharmacodynamic measurements were performed up to 48 hours thereafter. The effects of cilostazol on platelet aggregation, blood pressure, and heart rate were measured during the same period. The plasma concentration of cilostazol was measured with a validated HPLC method that entailed ultraviolet detection. The time courses of plasma cilostazol concentration, platelet aggregation, and cardiovascular effects were analyzed by means of pharmacokinetic-pharmacodynamic modeling with the program ADAPT II. RESULTS: The plasma concentration-time course followed a 2-compartment model. Mean peak concentration was 775 ng/ml approximately 3.65 hours after administration of cilostazol. The maximal effect on platelet aggregation was a 31.14% reduction 6.05 hours after administration. No significant difference in systolic blood pressure was found. The maximal increase in heart rate was 13.49%, whereas the maximal decrease in diastolic blood pressure was 29.51%. Both peak effects were detected approximately 6 hours after administration of the drug. Platelet aggregation and cardiovascular effects (change in diastolic blood pressure and heart rate) were analyzed with the effect-link sigmoid maximal effect model. CONCLUSION: This pharmacokinetic-pharmacodynamic model successfully described the relation between plasma concentration of cilostazol and the antiplatelet and cardiovascular effects of the drug.
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Woo et al. (2002) studied Healthy volunteers (n=20). Cilostazol was evaluated on Relation between plasma concentration of cilostazol and its antiplatelet and cardiovascular effects. A single 100 mg dose of cilostazol in healthy volunteers resulted in a mean peak concentration of 775 ng/ml, a 31.14% maximal reduction in platelet aggregation, and a 13.49% maximal increase in heart rate.
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