title: Insight to Pharmacokinetics of TKIs: Optimizing Practical Guidelines for Individualized Therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  This review highlights certain influence factors of TKIs clinical pharmacokinetics.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Wang
authors.forename: Chaoqin
authors.initials: C
authors.lastname: Zhong
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Hua
authors.affiliation: Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012. China.
authors.forename: Daoxin
authors.initials: D
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001786:Blood Glucose; D004032:Diet; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism; D057285:Precision Medicine; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001786:Blood Glucose; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases
keywords: Tyrosine kinase inhibitors (TKIs); chronic myeloid leukemia (CML); influence factors; pharmacokinetics; plasma concentration.; treatment