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와파린의 약물동태학에 니모디핀의 영향
Effects of Nimodipine on the Pharmacokinetics of Warfarin in Rats: A Possible Role of P-glycoprotein and CYP3A4 Inhibition by Nimodipine
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- 발행기관
- 한국임상약학회 바로가기
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- 간행물
- 한국임상약학회지 KCI 등재 바로가기
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- 통권
- 제23권 제3호 (2013.09)바로가기
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- 페이지
- pp.206-212
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- 저자
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- 언어
- 영어(ENG)
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- URL
- https://www.earticle.net/Article/A210488
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원문정보
초록
- 영어
- Purpose: The aim of this study was to investigate the effect of nimodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Methods: Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of nimodipine (0.5 or 2 mg/kg) in rats. The effect of nimodipine on the P-glycoprotein as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Results: Nimodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration (IC50) of 10.2 μM. Compared to those animals in the oral control group (warfarin without nimodipine), the area under the plasma concentration–time curve (AUC) of warfarin was significantly greater (0.5 mg/kg, P<0.05; 2 mg/kg, P<0.01) by 31.3-57.6%, and the peak plasma concentration (Cmax) was significantly higher (2 mg/kg, P<0.05) by 29.4% after oral administration of warfarin with nimodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.31- to 1.58-fold and the absolute bioavailability of warfarin with nimodipine was significantly greater by 64.1-76.9% compared to that in the control group (48.7%). In contrast, nimodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Conclusion: Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism rather than P-glycoprotein-mediated efflux by nimodipine.
목차
Abstract
MATERIALS AND METHODS
Chemicals and apparatus
Animal experiments
Oral and intravenous administration of warfarin
HPLC assay
CYP inhibition assay
Rhodamine-123 retention assay
Pharmacokinetic analysis
Statistical analysis
RESULTS
Inhibitory effect of nimodipine on CYP3A4 activity
Rhodamine-123 retention assay
Effect of nimodipine on the pharmacokinetics of warfarin after oral administration
Effect of nimodipine on the pharmacokinetics of warfarin after intravenous administration
DICUSSION
ACKNOWLEDGEMENT
REFERENCES
저자
간행물 정보
발행기관
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- 발행기관명
- 한국임상약학회 [Korean College of Clinical Pharmacy]
- 설립연도
- 1
- 분야
- 의약학>약학
- 소개
- 합리적 약물치료(rational pharmacotherapy)의 보장 및 증진을 궁극목적으로 하며 이를 달성하기 위해 임상약학의 발전과 회원 상호간의 친목을 도모한다.
간행물
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- 간행물명
- 한국임상약학회지 [Korean Journal of Clinical Pharmacy]
- 간기
- 계간
- pISSN
- 1226-6051
- 수록기간
- 1991~2026
- 등재여부
- KCI 등재
- 십진분류
- KDC 518 DDC 615
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