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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 493 - 497 (5page)
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초록· 키워드
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The aim of this study was to investigate the effect of amlodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of amlodipine (0.1 or 0.4 mg/kg) in rats. The effect of amlodipine on the P-glycoprotein (P-gp) as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Amlodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of 9.1 ${\mu}M$. Compared to those animals in the oral control group (warfarin without amlodipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (0.1 mg/kg, p<0.05; 0.4 mg/kg, p<0.01) by 26.5-53.5%, and the peak plasma concentration ($C_{max}$) was significantly higher (0.4 mg/kg, p<0.05) by 26.2% after oral administration of warfarin with amlodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.26- to 1.53-fold and the absolute bioavailability of warfarin with amlodipine was significantly greater by 61.7-72.5% compared to that in the control group (47.4%). In contrast, amlodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver rather than renal elimination and P-gp by amlodipine.
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참고문헌 (25)
참고문헌 신청
Abernethy, D. R / 1991 / Selective inhibition of warfarin metabolism by diltiazem in humans / J. Pharmacol. Exp. Ther 257:411~415
Abernethy, D. R / 1992 / Pharmacokinetics and pharmacodynamics of amlodipine / Cardiology 80:31~36
Benet, L. Z / 2003 / Transporter-enzyme interactions: implications for predicting drug-drug interactions from in vitro data / Curr. Drug Metab 4:393~398
Choi, J. S / 2006 / Phatmacokinetics interaction between Fluvastatin and Diltiazem in rats / Biopharm. Drug Dispos 27:437~441
Choi, D. H / 2008 / Effect of atrovastatin on intravenous and oral pharmacokinetics of verapamil in rats / Drug Dispos 29:45~50
Abernethy, D. R / 1992 / Pharmacokinetics and pharmacodynamics of amlodipine / Cardiology 80:31~36
Benet, L. Z / 2003 / Transporter-enzyme interactions: implications for predicting drug-drug interactions from in vitro data / Curr. Drug Metab 4:393~398
Choi, J. S / 2006 / Phatmacokinetics interaction between Fluvastatin and Diltiazem in rats / Biopharm. Drug Dispos 27:437~441
Choi, D. H / 2008 / Effect of atrovastatin on intravenous and oral pharmacokinetics of verapamil in rats / Drug Dispos 29:45~50
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