니페디핀과 파크리탁셀의 약물동태학적 상호작용

Pharmacokinetic Interaction between Nifedipine and Paclitaxel in Rats

The purpose of this study was to investigate the effect of coadministration and 3 days-pretreatmemt of nifedipine (2, 10 mg/kg) on the pharmacokinetic parameters and bioavailability of paclitaxel (50 mg/kg) after oral administration in rats. Coadministration of nifedipine with paclitaxel did alter the Cmax (l15±29 ng/ml without nifedipine; 135±35 ng/ml with nifedipine (10 mg/kg); p<0.05) and AUC (188±459 ng/ml·hr without nifedipine; 2546±642 ng/ml·hr with nifedipine; p<0.05). Three days treatment of nifedipine on the prior to paclitaxel administration increased the t1/2[9.90±2.47 hr without nifedipine; 12.37±3.12 hr with nifedipine (2 mg/kg); 12.83±3.32 hr with nifedipine (10 mg/ml); p<0.05] and AUC [1833 ±459 ng/ml·hr without nifedipine; 2663±648 ng/ml·hr with nifedipine (2 mg/kg); 3006±734 ng/ml·hr with nifedipine (10 mg/ml); p<0.05]. Drug interaction between nifedipine and paclitaxel decreased the elimination rate constant and increased the oral bioavailability of paclitaxel. On the basis of the results of this study, it might be considered that nifedipine may inhibit cytochrome P45O, which are engaged in paclitaxel metabolism, result in increased t1/2 and AUC of paclitaxel. Howeverl further study should be conducted to clarify the roles of cytochrome P45O and P-glycoprotein on paclitaxel bioavailability with/or without nifedipine.