Wang Ruiqing, Zhong Chaoqin, Zhang Chen, Hua Mingqiang, Ma Daoxin
Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012. China.
Curr Drug Metab. 2017;18(3):199-206. doi: 10.2174/1389200218666170116113705.
Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavailability and stable blood concentration in humans. TKIs pharmacokinetics has close relationships with the clinical response and clinical treatment of CML.
We conducted a systematic PubMed search to look for studies relating to TKIs pharmacokinetics with proper inclusion/exclusion criteria. After looking through a large number of references, we investigated that different generations of TKIs could be influenced by many factors. We chose some typical factors which were closely linked to the common treatment of CML. These factors contain daily dose, diet, individual variability, drug-drug interaction, drugs resistance and drug withdrawal.
By summarizing up these influence factors, we hope it can make a contribution to clinical therapy. Above all, the relationship between influence factors and the clinical therapeutic effect is the key point that our research pays attention to.
This review highlights certain influence factors of TKIs clinical pharmacokinetics.
酪氨酸激酶抑制剂(TKIs)是广泛使用的药物,在降低BCR-ABL1酪氨酸激酶活性方面具有高可用性,因此它们在慢性髓性白血病(CML)的治疗中发挥着不可或缺的作用。伊马替尼、达沙替尼和尼洛替尼已被证明在人体中具有绝对生物利用度和稳定的血药浓度。TKIs的药代动力学与CML的临床反应和临床治疗密切相关。
我们在PubMed上进行了系统检索,以寻找符合适当纳入/排除标准的与TKIs药代动力学相关的研究。在查阅大量参考文献后,我们研究发现不同代的TKIs可能受到多种因素的影响。我们选择了一些与CML常见治疗密切相关的典型因素。这些因素包括每日剂量、饮食、个体差异、药物相互作用、耐药性和停药。
通过总结这些影响因素,我们希望能为临床治疗做出贡献。最重要的是,影响因素与临床治疗效果之间的关系是我们研究关注的重点。
本综述强调了TKIs临床药代动力学的某些影响因素。