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The aim of this study was to investigate the effect of fluvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with fluvastatin (0.5 and 1.5 mg/kg). Compared with the control (given nicardipine alone), coadministration of fluvastatin (0.5 mg/kg) significantly (p<0.01) increased the area under the plasma concentration (AUC) and peak plasma concentration (Cmax) of nicardipine. The toral plasma clearance (CL/F) of nicardipine was decreased significantly (p<0.01, 0.5 mg/kg) compared to the control group. The relative bioavailability (RB%) of nicardipine increased from 1.23- to 1.68-fold. However there were no significant changes in tmax, Kel and t1/2 of nicardipine. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism of nicardipine are competitively inhibited by fluvastatin. Based on these results, the concurrent use of fluvastatin significantly enhanced the oral exposure of nicardipine in rats.
목차
ABSTRACT 연구방법 시료, 시약 및 기기 실험동물 및 전처리 약물투여 및 혈액 채취 니카르디핀의 HPLC 분석 니카르디핀의 약물동태학적 분석 통계 처리 결과 고찰 결론 참고문헌