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Table 1 Pharmacokinetics of commonly used targeted cancer therapies

From: Management of atrial fibrillation in patients taking targeted cancer therapies

Tyrosine Kinase Inhibitors Molecular Target(s) FDA-Approved Indications Clinically Significant Drug Metabolism/Elimination Clinically Significant Adverse Effects
Afatinib ErbB family (EGFR, HER-2,-4) NSCLC P-gp substrate  
Axitinib VEGFR-1,-2,-3 RCC CYP3A4 substrate  
Bosutinib BCR-ABL, SRC family (SRC, LYN, HCK), c-KIT, PDGFR CML CYP3A4 substrate; P-gp inhibitor QT prolongation
Cabozantinib HGFR, RET, VEGFR-1, −2, −3, KIT, FLT3, TIE-2, TRKB, AXL Medullary thyroid cancer CYP3A4 substrate  
Ceritinib ALK, IGF-1R, InsR, ROS1 NSCLC CYP3A4 substrate & strong inhibitor; P-gp substrate QT prolongation
Crizotinib ALK, HGFR, RON NSCLC CYP3A4 substrate & moderate inhibitor; CYP2B6 moderate inhibitor; P-gp substrate and inhibitor QT prolongation
Dasatinib SRC family (SRC, LCK, YES, FYN), BCR-ABL, c-KIT, EPH-A2, PDGFR-β ALL, CML CYP3A4 substrate & weak inhibitor QT prolongation
Erlotinib EGFR NSCLC, Pancreatic cancer CYP3A4 substrate  
Gefitinib EGFR NSCLC CYP3A4 substrate; CYP2D6 substrate  
Ibrutinib BTK CLL, MCL, WM CYP3A4 substrate; P-gp inhibitor  
Imatinib BCR-ABL, c-KIT, PDGFR, SCF ALL, CEL, CML, GIST, ASM, DFSP, MDS/MPD CYP3A4 substrate & moderate inhibitor; P-gp substrate  
Lapatinib EGFR, HER2 Breast cancer CYP3A4 substrate; CYP2C8 moderate inhibitor; P-gp substrate & inhibitor QT prolongation
Lenvatinib VEGFR-1,-2,-3, FGFR-1,-2,-3,-4, PDGF-α, KIT, RET Thyroid cancer   QT prolongation
Nilotinib BCR-ABL, PDGFR, c-KIT CML CYP3A4 substrate & moderate inhibitor; CYP2D6 moderate inhibitor; CYP2C8 moderate inhibitor; P-gp inhibitor QT prolongation
Osimertinib EGFR NSCLC CYP3A4 substrate; BRCP inhibitor QT prolongation
Pazopanib VEGFR-1,-2,-3, PDGFR-α,-β, FGFR-1,-3, c-KIT, IL-2 inducible TcK, Lck, c-Fms RCC, STS CYP3A4 substrate; P-gp substrate QT prolongation
Regorafenib VEGFR-1,-2,-3, KIT, PDGFR-α,-β, RET, FGFR-1,-2, TIES2, DDR2, TrkA, EPH-A2, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, ABL Colorectal cancer, GIST CYP3A4 substrate Bradycardia
Ruxolitinib JAK-1,-2 Myelofibrosis, Polycythemia vera CYP3A4 substrate Bradycardia
Sorafenib RAF, VEGFR-1,-2,-3, PDGFR-β, c-KIT, FLT-3, RET, RET/PTC RCC, HCC, Thyroid carcinoma CYP2C9 moderate inhibitor; CYP2B6 moderate inhibitor QT prolongation
Sunitinib PDGFR-α,-β, VEGFR-1,-2,-3, FLT3, CSF-1R, RET RCC, GIST, PNET CYP3A4 substrate; P-gp inhibitor QT prolongation
Vandetanib EGFR, VEGFR, RET, BRK, TIES2, EPH, SRC Medullary thyroid cancer P-gp inhibitor QT prolongation
  1. ALK anaplastic lymphoma kinase, BCR-ABL fusion gene, BRAF B-Raf Proto-Oncogene, Serine/Threonine Kinase, BRK protein tyrosine kinase 6, BTK Bruton’s Tyrosine Kinase, c-Fms transmembrane glycoprotein receptor tyrosine kinase, c-KIT cytokine receptor, CSF-1R colony-stimulating factor type 1, DDR2 discoidin domain receptor 2, EGFR epidermal growth factor receptor, EPH Ephrin Receptor, ErbB family of tyrosine kinase inhibitors, FGFR fibroblast growth factor receptor, FLT FMS-like Tyrosine Kinase, HCK Hemopoietic cell kinase, HER human epidermal growth factor receptor, HGFR hepatocyte growth factor receptor, IGF-1R insulin-like growth factor 1 receptor. IL-2 inducable, TCK interleukin-2 receptor inducible T-cell Kinase, InsR insulin receptor, JAK Janus Associated Kinases, Lck Leukocyte-specific Protein Tyrosine Kinase, PDGFR platelet-derived growth factor receptor, PTK protein tyrosine kinase 2 beta, RET “Rearranged During Transfection”, RON Recepteur d’Origine Nantais, SCF stem cell factor, TIE Tyrosine Kinase with Immunoglobulin-like and EGF-like Domains, VEGFR vascular endothelial growth receptor, ALL acute lymphoblastic leukemia, ASM aggressive systemic mastocytosis, CEL chronic eosinophilic leukemia, CML chronic myeloid leukemia, DFSP Dermatofibrosarcoma Protuberans, GIST gastrointestinal stromal tumor, HCC hepatocellular carcinoma, MCL mantle cell lymphoma, MDS/MPD myelodysplastic syndrome/myeloproliferative disease, NSCLC non-small cell lung cancer, PNET pancreatic neuroendocrine tumor, RCC renal cell carcinoma, STS soft tissue sarcoma, WM Waldenstrom’s Macroglobulinemia, BRCP breast cancer resistance protein, P-gp P-glycoprotein