Platelet aggregometry in the presence of PGE(1) provides a reliable method for cilostazol monitoring.

INTRODUCTION

Cilostazol has been shown to be effective for prevention and treatment of cerebral infarction. However, there appears to be no widely accepted method appropriate for monitoring cilostazol. We attempted to establish an assay system for cilostazol monitoring, using platelet aggregation induced by arachidonic acid (AA) in the presence of PGE(1) which upregulates intracellular cyclic AMP.

METHODS

Blood was drawn from stroke patients before and after cilostazol intake. AA-induced platelet aggregation after pretreatment with 0~30nM PGE(1) for 2minutes was measured by light transmittance aggregometry.

RESULTS

AA-induced platelet aggregation was 73.1±2.2% in the absence of PGE(1), and pretreatment with 30nM PGE(1) had virtually no inhibitory effect on platelet aggregation prior to cilostazol intake. In contrast, after cilostazol intake, 30nM PGE(1) significantly inhibited platelet aggregation to 12.7±4.5% (p=7.8×10(-11)) , while in the absence of PGE(1) platelet aggregation remained similar to that of prior-to-cilostazol value (70.6±3.5%). The plasma concentration of cilostazol ranged from 0.55 to 3.51μM. In the presence of 30nM PGE(1), all the patients with cilostazol concentrations exceeding 1μM had their platelet aggregation inhibited almost completely. ROC analysis suggests that AA-induced platelet aggregation in the presence of 30nM PGE(1) had the excellent sensitivity (90.5%) and specificity (88.4%) for monitoring cilostazol.

CONCLUSIONS

AA-induced platelet aggregation in the presence of 30nM PGE(1) could give good estimate on plasma concentrations of cilostazol. It is suggested that this system is a good tool for monitoring cilostazol.