中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors

文献类型：期刊论文

作者Zhu, Yun-Ting1; Teng, Zan2,3; Zhang, Yi-Fan1; Li, Wei1; Guo, Li-Xia1; Liu, Yun-Peng2,3; Qu, Xiu-Juan2,3; Wang, Quan-Ren4; Mao, Si-Yuan4; Chen, Xiao-Yan1
刊名DRUG DESIGN DEVELOPMENT AND THERAPY
出版日期2020
卷号14页码:1963-1970
关键词apatinib drug-drug interaction CYP3A4 CYP2C9 nifedipine warfarin
ISSN号1177-8881
DOI10.2147/DDDT.S237301
通讯作者Zhang, Yi-Fan(yfzhang@simm.ac.cn) ; Zhong, Da-Fang(dfzhong@simm.ac.cn)
英文摘要Background and Purpose: Apatinib is a small-molecule tyrosine kinase inhibitor for the treatment of recurrent or progressive advanced-stage gastric adenocarcinoma or gastroeso-phageal 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. 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, respectively. The pharmacokinetics of nifedipine and warfarin in the absence or presence of apatinib was, respectively, investigated. Results: Compared with the single oral administration, coadministration with apatinib contributed to the significant increases of AUC(0) (48)h and C-max 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(0-t) and C-max of S-warfarin by 92% (90% CI 1.68-2.18) and 24% (90% CI 1.10-1.39), respectively. 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.
WOS关键词DRUG-DRUG INTERACTIONS ; S-WARFARIN ; CLEARANCE
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000534380400001
出版者DOVE MEDICAL PRESS LTD
源URL[http://119.78.100.183/handle/2S10ELR8/279997]  
专题新药研究国家重点实验室
通讯作者Zhang, Yi-Fan; Zhong, Da-Fang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
2.China Med Univ, Dept Med Oncol, Hosp 1, Shenyang, Peoples R China
3.China Med Univ, Key Lab Anticanc Drugs & Biotherapy Liaoning Prov, Hosp 1, Shenyang, Peoples R China
4.Jiangsu Hengrui Med Co Ltd, Dept Clin Res & Dev, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Yun-Ting,Teng, Zan,Zhang, Yi-Fan,et al. Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2020,14:1963-1970.
APA Zhu, Yun-Ting.,Teng, Zan.,Zhang, Yi-Fan.,Li, Wei.,Guo, Li-Xia.,...&Zhong, Da-Fang.(2020).Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors.DRUG DESIGN DEVELOPMENT AND THERAPY,14,1963-1970.
MLA Zhu, Yun-Ting,et al."Effects of Apatinib on the Pharmacokinetics of Nifedipine and Warfarin in Patients with Advanced Solid Tumors".DRUG DESIGN DEVELOPMENT AND THERAPY 14(2020):1963-1970.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。