Journal of Korean Society for Clinical Pharmacology and Therapeutics (임상약리학회지)

Korean Society for Clinical Pharmacology and Therapeutics (대한임상약리학회)
권호 표지

Evaluation of Pharmacokinetics and Tolerability of Eplerenone after Multiple Oral Doses of 100 mg in Healthy Korean Volunteers

건강한 한국인 피험자에서 Eplerenone 100 mg 반복 경구 투여 후의 약동학적 특성 및 내약성 평가

  • Yoon, Seong-Hae (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Lee, Seung-Hwan (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Oh, Dal-Seok (Korea Institute of Oriental Medicine) ;
  • Lim, Kyoung-Soo (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Shin, Sang-Goo (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Jang, In-Jin (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital) ;
  • Yu, Kyung-Sang (Department of Pharmacology and Clinical Pharmacology, Seoul National University College of Medicine and Hospital)
  • 윤성혜 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 이승환 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 오달석 (한국한의학연구원) ;
  • 임경수 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 신상구 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 장인진 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과) ;
  • 유경상 (서울대학교 의과대학 약리학교실 및 서울대학교병원 임상약리학과)
  • Received : 2011.11.29
  • Accepted : 2011.12.27
  • Published : 2011.12.30
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Abstract

Background: Eplerenone is a selective mineralocorticoid receptor antagonist which effectively blocks mineralocorticoid receptors in various tissues throughout the body. The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients post acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The aim of this study was to evaluate pharmacokinetic characteristics and tolerability after multiple oral administration of eplerenone 100 mg for 7 days in healthy Korean volunteers. Methods: A double-blind, randomized, placebo-controlled, parallel study was conducted in 22 healthy Korean subjects. Healthy males and females between age of 20 and 55 years were enrolled. Each subject received 100 mg eplerenone (N=16) or placebo (N=6) for 7 days. Blood samples for pharmacokinetic parameter determination on day 7 were collected pre-dose and up to 36 hours after last drug administration. Adverse events were reported throughout the treatment period. Results: The steady-state concentration of eplerenone reached after multiple administration of eplerenone 100 mg for 7 days. The mean eplerenone Cmax of 1620.1 ng/mL was obtained at 1.0 hour (range 0.5 to 2 hours). The mean $AUC_{0-24h,ss}$ at day 7 was 8763.6 ng/mL*h. The mean oral clearance and mean terminal half-life of eplerenone were 13.0 L/h and 3.4 hours. There were some drug-related mild adverse events after eplerenone administration, but all adverse events recovered without any treatment. Conclusion: In this study, the pharmacokinetic parameters after multiple oral doses of eplerenone 100 mg for 7 days were evaluated and eplerenone at these doses were well tolerated in healthy Korean subjects.

Keywords

Acknowledgement

Supported by : 파마시아코리아(주)(Pfizer)

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