Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors

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	Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors
	Ding Juefang; Zhong Dafang
刊名	Acta Pharmaceutica Sinica
	2013
卷号	48 期号:7 页码:1080-1090
关键词	tyrosine kinase inhibitor pharmacokinetics drug-drug interaction
ISSN号	0513-4870
其他题名	小分子酪氨酸激酶抑制剂的临床药代动力学研究进展
文献子类	Review
英文摘要	Human protein tyrosine kinases play an essential role in carcinogenesis and have been recognized as promising drug targets. By the end of 2012, eight small molecule tyrosine kinase inhibitors (TKIs) have been approved by State Food and Drug Administration of China for cancer treatment. In this paper, the pharmacokinetic characteristics (absorption, distribution, metabolism and excretion) and drug-drug interactions of the approved TKIs are reviewed. Overall, these TKIs reach their peak plasma concentrations relatively fast; are extensively distributed and highly protein bound (<90%); are primarily metabolized by CYP3A4; most are heavily influenced by CYP3A4 inhibitors or inducers except for sorafenib; are mainly excreted with feces and only a minor fraction is eliminated with the urine; and are substrate of the efflux transporters ABCB1 (P-gp) and ABCG2 (BCRP). Additionally, many of the TKIs can inhibit some CYP450 enzymes, UGT enzymes, and transporters. Gefitinib, erlotinib, dasatinib, and sunitinib are metabolized to form reactive metabolites capable of covalently binding to biomolecules.
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:4882824
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/267773]
专题	上海药物代谢研究中心
通讯作者	Zhong Dafang
作者单位	Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China.
推荐引用方式 GB/T 7714	Ding Juefang,Zhong Dafang. Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors[J]. Acta Pharmaceutica Sinica,2013,48(7):1080-1090.
APA	Ding Juefang,&Zhong Dafang.(2013).Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors.Acta Pharmaceutica Sinica,48(7),1080-1090.
MLA	Ding Juefang,et al."Clinical pharmacokinetics of small molecule tyrosine kinase inhibitors".Acta Pharmaceutica Sinica 48.7(2013):1080-1090.