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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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Abstract

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.

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Acknowledgments

The study was supported by a grant received from Science and Engineering Research Board, Government of India (SERB- SB/FT/LS-147/2012).

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Authors and Affiliations

  1. Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India

    Jose Francis, Rajan Sundaram & Suresh Chandra Pradhan

  2. Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India

    Biswajit Dubashi

  3. Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605 006, India

    Adithan Chandrasekaran

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  1. Jose Francis
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  2. Biswajit Dubashi
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  3. Rajan Sundaram
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  4. Suresh Chandra Pradhan
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Corresponding author

Correspondence to Biswajit Dubashi.

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Francis, J., Dubashi, B., Sundaram, R. et al. 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. Cancer Chemother Pharmacol 76, 1185–1189 (2015). https://doi.org/10.1007/s00280-015-2905-6

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  • DOI: https://doi.org/10.1007/s00280-015-2905-6

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