도토리 추출물 투여 후 갈산의 집단약동학 분석

Population Pharmacokinetic Analysis of Gallic Acid after Acorn Extract Administration

  • 이종태 (가톨릭대학교 서울성모병원 임상약리학과) ;
  • 도기찬 (가톨릭대학교 서울성모병원 임상약리학과) ;
  • 김지면 (가톨릭중앙의료원 임상연구지원센터) ;
  • 전상일 (가톨릭대학교 서울성모병원 임상약리학과) ;
  • 한승훈 (가톨릭대학교 서울성모병원 임상약리학과)
  • Lee, Jong-Tae (Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, the Catholic University of Korea) ;
  • Doh, Ki-Chan (Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, the Catholic University of Korea) ;
  • Kim, Ji-Myon (Clinical Research Coordinating Center, Catholic Medical Center) ;
  • Jeon, Sang-Il (Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, the Catholic University of Korea) ;
  • Han, Seung-Hoon (Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, the Catholic University of Korea)
  • 투고 : 2010.12.15
  • 심사 : 2010.12.28
  • 발행 : 2010.12.30

초록

Background: Recently, researches on the pharmacological activity of natural substance are increasing. Acorn is one of promising candidates which is expected to exert anti-aging effects through anti-oxidant activity of gallic acid (GA). Methods: Crude extract was obtained from acorn which was harvested in Korea, 2009. After random allocation of 18 subjects into different dose groups (1g, 2g and 4g daily), the extract was given orally for 21 days. Full pharmacokinetic studies (0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr after dose) were done after the first and last doses. The LC/MS/MS system was used to determine the GA in the extract and plasma samples. The results were analyzed using mixed effect methods NONMEM (Ver.6.2). Results: GA content in the extract was 0.27% (m/m). An one-compartment model was used to describe the PK property. Oral Clearance (CL/F) was 153 L/hr with the between-subject variability (BSV, as RSV %) of 44.5%. The estimated volume of distribution (V/F) was 231 L with the BSV of 37.0%. The population estimates of absorption rate constant (Ka) was $3.23\;hr^{-1}$ and the relative bioavailability of 4g dose group was 75.4% compared to the other groups. Conclusion: Population pharmacokinetic parameters for gallic acid were successfully estimated. According to the parameters, it was expected that gallic acid would not be accumulated after repeated once-daily dosing and the extent of gallic acid absorption would be limited in the 4g dose group.

키워드

과제정보

연구 과제 주관 기관 : 농촌진흥청

참고문헌

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