Zhu, Yun-Ting published the artcileEffects of apatinib on the pharmacokinetics ofnifedipine and warfarin in patients with advancedsolid tumors, Formula: C17H18N2O6, the main research area is CYP2C9; CYP3A4; apatinib; drug-drug interaction; nifedipine; warfarin.
Background and Purpose: Apatinib is a small-mol. tyrosine kinase inhibitor for the treatment of recurrent or progressive advanced-stage gastric adenocarcinoma or gastroesophageal junction cancer. The in vitro inhibition studies suggested that apatinib exerted potent inhibition on CYP3A4 and CYP2C9. To evaluate the potential of apatinib as a perpetrator in CYP450-based drug-drug interactions in vivo, nifedipine and warfarin were, resp., selected in the present study as the probe substrates of CYP3A4 and CYP2C9 for clin. drug-drug interaction studies. Since hypertension and thrombus are common adverse effects of vascular targeting anticancer agents, nifedipine and warfarin are usually coadministered with apatinib in clin. practice. Methods: A single-center, open-label, single-arm, and self-controlled trial was conducted in patients with advanced solid tumors. The patients received a single dose of 30 mg nifedipine on Day 1/14 and a single dose of 3 mg warfarin on Day 3/16. On Day 9-21, the subjects received a daily dose of 750 mg apatinib, resp. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, resp., investigated. Results: Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC0-48h and Cmax of nifedipine by 83% (90% confidence interval [CI] 1.46-2.31) and 64% (90% CI 1.34-2.01), resp. Similarly, coadministration with apatinib contributed to the significant increases of AUC0-t and Cmax of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), resp. Conclusion: Concomitant apatinib administration resulted in significant increases in systemic exposure to nifedipine and S-warfarin. Owing to the risk of pharmacokinetic drug-drug interactions based on CYP3A4/CYP2C9 inhibition by apatinib, caution is advised in the concurrent use of apatinib with either CYP2C9 or CYP3A4 substrates.
Drug Design, Development and Therapy published new progress about CYP2C9; CYP3A4; apatinib; drug-drug interaction; nifedipine; warfarin. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.