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 |
ISSN号 | 0091-2700 |
关键词 | apatinib rifampin itraconazole drug-drug interaction pharmacokinetics |
DOI | 10.1002/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 |
出版者 | WILEY |
WOS记录号 | WOS:000424394300010 |
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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