J Korean Soc Clin Pharmacol Ther.
2011 Dec;19(2):73-83.
Influence of Simvastatin on Pharmacokinetics/Pharmacodynamics of Aspirin after Oral Co-administration in Healthy Volunteers
- Affiliations
-
- 1Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine andhospital, South Korea. ksyu@snu.ac.kr
- 2Clinical Research Coordinating Center, Catholic Medical Center, Seoul, South Korea.
- 3Department of Pharmacology, College of Medicine, the Catholic University of Korea, Seoul, South Korea.
Abstract
- 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 (Cmax) and the area under the concentration-time curve (AUC0-24). 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 Cmax and AUC0-24 for acetylsalicylic acid were 1.21 (1.04 - 1.42) and 1.28 (1.19 - 1.38), respectively. For salicylic acid, GMRs of Cmax and AUC0-24 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 +/- 8.8 % and 87.3 +/- 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.
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