건강한 성인에서 아토르바스타틴 경구흡수과정의 집단약동학 분석

Population Pharmacokinetic Analysis of the oral Absorption Process of Aforuastatin in Healthy Volunteers

  • 채홍석 (가톨릭대학교 강남성모병원 임상약리학과) ;
  • 안병진 (가톨릭대학교 강남성모병원 임상약리학과) ;
  • 한승훈 (가톨릭대학교 의과대학 약리학교실) ;
  • 김지면 (가톨릭중앙의료원 임상연구지원센터) ;
  • 도기찬 (가톨릭대학교 강남성모병원 임상약리학과) ;
  • 나현오 (가톨릭대학교 의과대학 약리학교실) ;
  • 임동석 (가톨릭대학교 의과대학 약리학교실)
  • Chae, Hong-Seok (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea) ;
  • Ahn, Byung-Jin (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea) ;
  • Han, Seung-Hoon (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea) ;
  • Kim, Ji-Myon (CMC Clinical Research Coordinatiry Center) ;
  • Doh, Ki-Chan (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea) ;
  • Lah, Hyon-Oh (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea) ;
  • Yim, Dong-Seok (Department of Pharmacology and Department of Clinical Pharmacology and Therapeutics, the Catholic University of Korea)
  • 발행 : 2008.12.30

초록

Backgrounds: Atorvastatin which has a highly variable pharmacokinetic profileoften shows double peaks. However, in most cases it has been regarded as a noise or assay error. In this study we compared 4 different absorption models (zero order, $1^{st}$ order, combined and parallel absorption model) to determine which model best describes the absorption process. Methods: Plasma atorvastatin data of 57 healthy subjects from two bioequivalence studies were used. Concentrations were measured up to 48 hours after drug administration. Mixed effect analysis to compare the 4 absorption models was performed using NONMEM version 6.0. Results: The absorption process was best described bycombined absorption model. CL/F and Vd/F were 400L/hand 779L, respectively, and KA and D were $0.09\;hr^{-1}$ and $0.53\;hr^{-1}$, respectively. Conclusion: Although the combined absorption model did not fully describe the double peaks, this study demonstrated that absorption models other than simple first or zero order absorption are necessary to describe the double peaks phenomenon.

키워드