Genetic Polymorphism on the Pharmacokinetics and Pharmacodynamics of Platelet-derived Growth Factor Receptor (PDGFR) Kinase Inhibitors

Platelet-derived Growth Factor Receptor (PDGFR) is one of the families of Receptor Tyrosine Kinases (RTKs), which have attracted increasing attention as a potential target of antitumor therapy in cancer. PDGFR family members consist of PDGFR-α, PDGFR-β, CSF-1R, KIT and FLT3. Tyrosine Kinase Inhibitors (TKIs) are a kind of small molecule inhibitors targeting RTKs. TKIs prevent and block vital pathways by targeting signaling molecules which are necessary for cell survival. At present, about 11 kinds of TKIs targeting PDGFR family members have been approved for the treatment of diseases like chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), etc. This review focuses on 11 PDGFR kinase inhibitors, including imatinib, sunitinib, regorafenib, sorafenib, pazopanib, axitinib, dasatinib, nilotinib, lenvatinib, cabozantinib and ponatinib. This article also provides an overview of: (1) general information on PDGFR kinase inhibitors; (2) pharmacokinetic 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 pharmacokinetics and pharmacodynamics of PDGFR kinase inhibitors.

Current drug metabolism. 2018 Jun 28 [Epub ahead of print]

Yi Qian, Lei Yu, Xue-Hui Zhang, Qing-Yun Yuan-Zi, Ping Zhao, Lu-Ning Sun, Yong-Qing Wang

Research Division of Clinical Pharmacology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029. China., Department of Pharmacy, Jiangsu Shengze Hospital, Suzhou 215228. China.