{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14"],"submitter":["Zhu YT"],"pubmed_abstract":["<h4>Background and purpose</h4>Apatinib is a small-molecule 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, respectively, selected in the present study as the probe substrates of CYP3A4 and CYP2C9 for clinical 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 clinical practice.<h4>Methods</h4>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, respectively. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, respectively, investigated.<h4>Results</h4>Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC<sub>0-48h</sub> and C<sub>max</sub> of nifedipine by 83% (90% confidence interval [CI] 1.46-2.31) and 64% (90% CI 1.34-2.01), respectively. Similarly, coadministration with apatinib contributed to the significant increases of AUC<sub>0-t</sub> and C<sub>max</sub> of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), respectively.<h4>Conclusion</h4>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."],"journal":["Drug design, development and therapy"],"pagination":["1963-1970"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7246325"],"repository":["biostudies-literature"],"pubmed_title":["Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors."],"pmcid":["PMC7246325"],"pubmed_authors":["Li W","Guo LX","Zhong DF","Liu YP","Zhang YF","Mao SY","Qu XJ","Zhu YT","Chen XY","Teng Z","Wang QR"],"additional_accession":[]},"is_claimable":false,"name":"Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors.","description":"<h4>Background and purpose</h4>Apatinib is a small-molecule 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, respectively, selected in the present study as the probe substrates of CYP3A4 and CYP2C9 for clinical 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 clinical practice.<h4>Methods</h4>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, respectively. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, respectively, investigated.<h4>Results</h4>Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC<sub>0-48h</sub> and C<sub>max</sub> of nifedipine by 83% (90% confidence interval [CI] 1.46-2.31) and 64% (90% CI 1.34-2.01), respectively. Similarly, coadministration with apatinib contributed to the significant increases of AUC<sub>0-t</sub> and C<sub>max</sub> of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), respectively.<h4>Conclusion</h4>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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020","modification":"2025-04-04T08:03:54.592Z","creation":"2020-06-19T07:03:54Z"},"accession":"S-EPMC7246325","cross_references":{"pubmed":["32546963"],"doi":["10.2147/DDDT.S237301"]}}