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Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole

文献类型：期刊论文

作者Liu, Xiaoyun3,4; Zhang, Yifan3; Chen, Qian2; Zhan, Yan3; Wang, Quanren1; Hu, Chaoying2; Yu, Chen2; Guo, Zitao3; Chen, Xiaoyan3,4; Zhong, Dafang3,4
刊名JOURNAL OF CLINICAL PHARMACOLOGY
出版日期2018-03
卷号58期号:3页码:347-356
关键词apatinib rifampin itraconazole drug-drug interaction pharmacokinetics
ISSN号0091-2700
DOI10.1002/jcph.1016
文献子类Article
英文摘要Apatinib is a small-molecule tyrosine kinase inhibitor that has been approved for the treatment of patients with advanced-stage gastric cancer or gastroesophageal junction cancer who have progressed or recurred after at least 2 kinds of systemic chemotherapy. In vitro data indicate that cytochrome P450 (CYP) 3A4 is the primary CYP isoenzyme involved in the metabolism of apatinib. Pharmacokinetic drug-drug interactions of apatinib and (1) a CYP3A4 inducer (rifampin) or (2) a CYP3A inhibitor (itraconazole) were clinically evaluated in healthy volunteers. Compared with the single administration of apatinib, its coadministration with rifampin resulted in a 5.6-fold plasma clearance (CL/F) and 83% decrease in plasma AUC(0-t) of apatinib. By contrast, coadministration with itraconazole reduced the CL/F of apatinib by 40% and increased its AUC(0-t) by 75%. In summary, a strong CYP3A4 inducer (rifampin) had a strong effect (>5-fold) on the clinical pharmacokinetics of apatinib, whereas a strong CYP3A inhibitor (itraconazole 100 mg once a day) had a weak effect (1.25-to 2-fold). Whether these effects are of clinical significance needs further research and information about the exposure-safety and exposure-efficacy relationship of apatinib.
WOS关键词INCREASES PLASMA-CONCENTRATIONS ; KETOCONAZOLE ; CLARITHROMYCIN ; TRANSPORTERS ; INHIBITION ; LOVASTATIN ; CANCER
资助项目National Natural Science Foundation of China[81521005]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000424394300010
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/279882]  
专题上海药物代谢研究中心
通讯作者Zhong, Dafang
作者单位1.Jiangsu Hengrui Med Co Ltd, Lianyungang, Peoples R China
2.Shanghai Xuhui Cent Hosp, Shanghai, Peoples R China;
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China;
4.Univ Chinese Acad Sci, Beijing, Peoples R China;
推荐引用方式
GB/T 7714		 Liu, Xiaoyun,Zhang, Yifan,Chen, Qian,et al. Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole[J]. JOURNAL OF CLINICAL PHARMACOLOGY,2018,58(3):347-356.
APA Liu, Xiaoyun.,Zhang, Yifan.,Chen, Qian.,Zhan, Yan.,Wang, Quanren.,...&Zhong, Dafang.(2018).Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole.JOURNAL OF CLINICAL PHARMACOLOGY,58(3),347-356.
MLA Liu, Xiaoyun,et al."Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole".JOURNAL OF CLINICAL PHARMACOLOGY 58.3(2018):347-356.

入库方式： OAI收割

来源：上海药物研究所

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