Influence of Simvastatin on Pharmacokinetics/Pharmacodynamics of Aspirin after Oral Co-administration in Healthy Volunteers

Background: Both aspirin and simvastatin are prescribed as treatments or prevention of cardiovascular diseases. The aim of this study was to investigate the influence of simvastatin on pharmacokinetics and pharmacodynamics of aspirin after oral co-administration in healthy subjects. Methods: Subjects were orally administered aspirin 100 mg for 7 days followed by co-administration of aspirin 100 mg and simvastatin 40 mg for 7 days once daily. A series of blood samples were collected before and till 24hours after drug administration on Day 1 (single-dose of aspirin), Day 7 (multiple-dose of aspirin) and Day 14 (multiple-dose of aspirin and simvastatin). The effects of simvastatin on pharmacokinetics of acetylsalicylic acid and salicylic acid were assessed with the 90 % confidence intervals (CIs) of thegeometric mean ratios (GMRs) of Day 14 over Day 7 for maximum plasma concentration ($C_{max}$) and the area under the concentration-time curve ($AUC_{0-24}$). Pharmacodynamics was assessed with maximal changes of platelet aggregation from baseline. Results: Twenty-fourhealthy men aged 20 to 36 years were enrolled and 23 of them completed the study. GMRs (90 % CIs) of $C_{max}$ and $AUC_{0-24}$ for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of $C_{max}$ and $AUC_{0-24}$ were 0.96 (0.91 - 1.00) and 1.00 (0.97 - 1.04), respectively. Maximal changes of platelet aggregation on Day 7 and Day 14 from baseline were not significantly different (p=0.41); $87.5{\pm}8.8$ % and $87.3{\pm}9.2$ %, respectively. Conclusion: Coadministration of simvastatin slightly increased the systemic exposure of acetylsalicylic acid with no changes of systemic exposure of salicylic acid or inhibition of platelet aggregation.

건강한 자원자에서 아스피린과 심바스타틴 병용투여 시, 심바스타틴이 아스피린의 약동학/약력학적 특성에 미치는 영향