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설효찬(Hyo Chan Seol),최준식(Jun Shik Choi) 대한약학회 2005 약학회지 Vol.49 No.5
The aim of this study is to investigate the effects of verapamil on the pharmacokinetics of tamoxifen follwing oral administration of tamoxifen with verapamil to rats. Tamoxifen (10mg/kg) was administered orally in the presence or absence of verapamil (1, 3 or 6 mg/kg). Compared to the control group (given tamoxifen alone), the presence of verapamil significantly (p〈 0.05 by 1mg/kg, p〈 0.01 by 3 and 6 mg/kg) increased the areas under the plasma concentration-time curve (AUC) and the peak concentrations (CMAX) of tamoxifen. Consequently, the relative bioavailability (RB%) of tamoxifen with verapamil was 1.6-2.1 fold highter than that of the control. But the time to reach peak concentration (TMAX) and the terminal half-life(t1/2) of tamoxifen were not altered significantly in the presence of verapamil. The increased AUC and CMAX of tamoxifen in the presence of verapamil might be associated with inhibition by verapamil of the P-glycoprotein and the firstpass metabolizing enzyme CYP3A4 in small intestinal mucosa. The drug interaction should be taken into consideration when tamoxifen is used to the patient with verapamil in the clinical setting.