지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
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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.
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참고문헌 (24)
참고문헌 신청
Benet LZ / 2003 / Transporter-enzyme interactions : implications for predicting drug?drug interactions from in vitro data / Curr Drug Metab 4 : 393 ~ 398
Crespi CL / 1997 / Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450 / Ana Biochem 248 : 188 ~ 190
Cummins CL / 2002 / Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4 / J Pharmacol Exp Ther 300 : 1036 ~ 1045
Darvari R / 2004 / Concentration dependency of modulatory effect of amlodipine on P-glycoprotein efflux activity of doxorubicin-a comparison with tamoxifen / J Pharm Pharmac
Epstein, M / 1990 / Effects of calcium antagonists on renal hemodynamics / Am J Kidney Dis 16 : 10 ~ 14
Crespi CL / 1997 / Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450 / Ana Biochem 248 : 188 ~ 190
Cummins CL / 2002 / Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4 / J Pharmacol Exp Ther 300 : 1036 ~ 1045
Darvari R / 2004 / Concentration dependency of modulatory effect of amlodipine on P-glycoprotein efflux activity of doxorubicin-a comparison with tamoxifen / J Pharm Pharmac
Epstein, M / 1990 / Effects of calcium antagonists on renal hemodynamics / Am J Kidney Dis 16 : 10 ~ 14
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