title: A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients.
abstract: OBJECTIVE
  Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and pharmacogenetic screening is warranted for better management of imatinib therapy. The present study was framed to explore the influence of common drug transporter gene polymorphisms of ABCB1, ABCG2, OCT1 and trough level concentration on commonly occurring adverse events in CML patients treated with imatinib mesylate.
  
  
  METHODS
  A total number of 111 patients in chronic phase (Philadelphia chromosome +ve) were included in the study. The plasma drug concentration of imatinib was estimated using LC-MS/MS method.
  
  
  RESULTS
  The mean ± SD trough level concentration of imatinib mesylate was found to be 1430.7 ± 438.7 ng/ml. The trough level concentration at steady state (Cmin.ss) was significantly higher in patients with grade 2-4 thrombocytopenia compared with patients without the adverse event (P value 0.033).
  
  
  CONCLUSIONS
  The drug level of imatinib in plasma correlates with the severity of thrombocytopenia, which adds to the utility of TDM in the management of CML patients.
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India.
authors.forename: Jose
authors.initials: J
authors.lastname: Francis
authors.affiliation: Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India. drbiswajitdm@gmail.com.
authors.forename: Biswajit
authors.initials: B
authors.lastname: Dubashi
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Sundaram
authors.affiliation: Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India.
authors.forename: Suresh Chandra
authors.initials: SC
authors.lastname: Pradhan
authors.affiliation: Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India.
authors.forename: Adithan
authors.initials: A
authors.lastname: Chandrasekaran
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002853:Chromatography, Liquid; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D053719:Tandem Mass Spectrometry; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D027702:Organic Cation Transporter 1; D000068877:Imatinib Mesylate
keywords: Imatinib; Pharmacogenetics; Therapeutic drug monitoring; Thrombocytopenia