Metabolism and pharmacokinetics of covalent tyrosine kinase inhibitors
10.16438/j.0513-4870.2018-0834
- VernacularTitle:共价酪氨酸激酶抑制剂的代谢和药动学
- Author:
Xiao-yun LIU
1
;
Xiao-yan CHEN
1
;
Da-fang ZHONG
1
Author Information
1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
covalent tyrosine kinase inhibitor;
metabolism;
pharmacokinetics;
human serum albumin;
covalently binding
- From:
Acta Pharmaceutica Sinica
2019;54(3):432-439
- CountryChina
- Language:Chinese
-
Abstract:
Covalent tyrosine kinase inhibitors (TKIs) can inhibit the signaling pathway of tumor cells by covalent binding with cysteine residues of target proteins, which has the advantages of high potency, extended duration of action and overcoming drug resistance. In this article, we will review the metabolism and pharmacokinetics of some covalent TKIs. Currently, the covalent TKIs approved by US food and drug administration (FDA) are afatinib, neratinib, dacomitinib, osimertinib, ibrutinib and acalabrutinib. Pyrotinib have been approved by National Medical Products Administration (NMPA) to reach the market recently. Covalent TKIs can covalently bind with plasma proteins, especially human serum albumin, thus effected the pharmacokinetics of these drugs.
