Cancer chemotherapy and pharmacology · 2015
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.
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Francis Jose, Dubashi Biswajit, Sundaram Rajan, Pradhan Suresh Chandra, Chandrasekaran Adithan
Аннотация
PURPOSE: 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).
CONCLUSION: 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.
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).
CONCLUSION: 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.
Предметные рубрики MeSH
ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2ATP-Binding Cassette TransportersAdolescentAdultAgedAllelesAntineoplastic AgentsChromatography, LiquidFemaleGene FrequencyGenotypeHumansImatinib MesylateLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLinear ModelsMaleMiddle AgedNeoplasm ProteinsOrganic Cation Transporter 1Polymorphism, Single NucleotideTandem Mass SpectrometryThrombocytopeniaTreatment OutcomeYoung Adult