Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Department of Pharmacy, Jiangsu Shengze Hospital, Suzhou 215228, China.
Curr Drug Metab. 2018;19(14):1168-1181. doi: 10.2174/1389200219666180629112943.
Platelet-derived Growth Factor Receptor (PDGFR) is a kind of Receptor Tyrosine Kinases (RTKs). PDGFR Tyrosine Kinase Inhibitors (TKIs) which are small molecule inhibitors targeting PDGFR prevent and block cell proliferation signal transduction pathways. Recently, there have been 11 TKIs (including imatinib, sunitinib, regorafenib, sorafenib, pazopanib, axitinib, dasatinib, nilotinib, lenvatinib, cabozantinib and ponatinib) targeting PDGFR approved by FDA for the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, renal cell carcinoma et al. Pharmacokinetics (PK) reflects the processes of drugs in body, while pharmacodynamics (PD) reflects the efficacy. Genetic polymorphisms of metabolizers and transporters contribute to highly inter-individual variability in PK and PD. This review aims to introduce the clinical applications, instruction and usage, PK, PD and pharmacogenetics of these PDGFR TKIs.
In vivo and in vitro studies about PDGFR TKIs were searched from PubMed. Data and information were analyzed and summarized.
The overview of (1) general information on PDGFR kinase inhibitors; (2) PK parameters of PDGFR kinase inhibitors; (3) metabolic enzymes and transporters of PDGFR kinase inhibitors; (4) main drug interactions of PDGFR kinase inhibitors; (5) adverse events of PDGFR kinase inhibitors; and (6) genetic polymorphism on PK and PD of PDGFR kinase inhibitors, was exhibited and discussed in this review.
This review summarized the general information, PK, metabolic enzymes and transporters, main drug interactions, adverse events and pharmacogenetics of FDA approved PDGFR TKIs. Studies showed that Single nucleotide polymorphisms of metabolic enzymes and transporters had influence on the PK and PD of PDGFR TKIs.
血小板衍生生长因子受体（PDGFR）是一种受体酪氨酸激酶（RTKs）。针对 PDGFR 的小分子抑制剂 PDGFR 酪氨酸激酶抑制剂（TKI）可预防和阻断细胞增殖信号转导途径。目前，FDA 已批准了 11 种针对 PDGFR 的 TKI（包括伊马替尼、舒尼替尼、瑞戈非尼、索拉非尼、帕唑帕尼、阿昔替尼、达沙替尼、尼洛替尼、仑伐替尼、卡博替尼和泊那替尼），用于治疗慢性髓性白血病、胃肠间质瘤、肾细胞癌等。药代动力学（PK）反映了药物在体内的过程，而药效学（PD）反映了疗效。代谢酶和转运体的遗传多态性导致 PK 和 PD 的个体间差异很大。本综述旨在介绍这些 PDGFR TKI 的临床应用、指导和使用、PK、PD 和药物遗传学。
从 PubMed 中搜索了关于 PDGFR TKI 的体内和体外研究。分析和总结了数据和信息。
本文综述了（1）PDGFR 激酶抑制剂的一般信息；（2）PDGFR 激酶抑制剂的 PK 参数；（3）PDGFR 激酶抑制剂的代谢酶和转运体；（4）PDGFR 激酶抑制剂的主要药物相互作用；（5）PDGFR 激酶抑制剂的不良反应；（6）PDGFR 激酶抑制剂 PK 和 PD 的遗传多态性，对这些内容进行了展示和讨论。
本综述总结了 FDA 批准的 PDGFR TKI 的一般信息、PK、代谢酶和转运体、主要药物相互作用、不良反应和药物遗传学。研究表明，代谢酶和转运体的单核苷酸多态性对 PDGFR TKI 的 PK 和 PD 有影响。
