Skip to main content

Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease

Abstract

Until now, no studies have addressed the use of dasatinib in hemodialysis patients. Herein, we report the case of a 73-year-old hemodialysis patient with chronic myeloid leukemia (CML) who was treated with dasatinib. For 5 years prior, the patient had received nilotinib for the treatment of CML. Regular hemodialysis was initiated due to progression of hypertensive nephrosclerosis, whereupon nilotinib was discontinued and the patient began receiving 100 mg dose of dasatinib once daily. On dialysis days, dasatinib was administered immediately after completion of dialysis. Four months after starting dasatinib, we performed a pharmacokinetic study. The plasma concentrations of dasatinib before, immediately, and 2 h after the completion of hemodialysis were 7.4, 6.1, and 59.5 ng/mL, respectively. Ultrasound cardiography revealed a gradual decline in ejection fraction during dasatinib therapy. Because the patient’s dasatinib trough concentration was higher (6.1 ng/mL) than the target level (1.5 ng/mL), we suspected the development of dasatinib-related heart dysfunction; thus, dasatinib was discontinued 6 months after its initiation. We concluded that hemodialysis patients are potentially vulnerable to the cardiotoxic effects of dasatinib; monitoring of cardiac function and plasma drug concentration may thus be useful in assessing their condition.

This is a preview of subscription content, access via your institution.

References

  1. Miura M, Takahashi N. Routine therapeutic drug monitoring of tyrosine kinase inhibitors by HPLC-UV or LC-MS/MS methods. Drug Metab Pharmacokinet. 2016;31:12–20.

    CAS  Article  Google Scholar 

  2. Christopher LJ, Cui D, Li W, Barros A, Arora VK, Zhang H, et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos. 2008;36:1357–64.

    CAS  Article  Google Scholar 

  3. Mizuta S, Sawa M, Tsurumi H, Matsumoto K, Miyao K, Hara T, et al. Plasma concentrations of dasatinib have a clinical impact on the frequency of dasatinib dose reduction and interruption in chronic myeloid leukemia: an analysis of the DARIA 01 study. Int J Clin Oncol. 2018;23:980–8.

    CAS  Article  Google Scholar 

  4. Rousselot P, Mollica L, Etienne G, Bouchet S, Guerci A, Nicolini FE, et al. Pharmacologic monitoring of dasatinib as first line therapy in newly diagnosed chronic phase chronic myelogenous leukemia (CP-CML) identifies patients at higher risk of pleural effusion: a sub-analysis of the OPTIM-dasatinib trial. Blood. 2012;120:3770.

    Article  Google Scholar 

  5. Dreisbach AW, Lertora JJ. The effect of chronic renal failure on drug metabolism and transport. Expert Opin Drug Metab Toxicol. 2008;4:1065–74.

    CAS  Article  Google Scholar 

  6. Yeung CK, Shen DD, Thummel KE, Himmelfarb J. Effects of chronic kidney disease and uremia on hepatic drug metabolism and transport. Kidney Int. 2014;85:522–8.

    CAS  Article  Google Scholar 

  7. Rangaswami J, Mccullough PA. Heart failure in end-stage kidney disease: pathophysiology, diagnosis, and therapeutic strategies. Semin Nephrol. 2018;38:600–17.

    Article  Google Scholar 

  8. Brave M, Goodman V, Kaminskas E, Farrell A, Timmer W, Pope S, et al. Sprycel for chronic myeloid leukemia and Philadelphia chromosome–positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate. Clin Cancer Res. 2008;14:352–9.

    CAS  Article  Google Scholar 

Download references

Funding

NT reports grants and personal fees obtained from Novartis Pharmaceuticals, personal fees from Bristol-Myers Squibb, grants and personal fees from Pfizer, grants and personal fees from Otsuka Pharmaceutical, grants from Kyowa Hakko Kirin, grants from Astellas Pharma, grants from Chugai Pharmaceutical, grants from Asahi Kasei Pharma, grants from Ono Pharmaceutical, and grants from Eisai Pharmaceuticals, which are all unrelated the study reported herein.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jinichi Mori.

Ethics declarations

Conflict of interest

The other authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mori, J., Oshima, K., Tanimoto, T. et al. Pharmacokinetics of dasatinib in a hemodialysis patient with chronic myeloid leukemia and chronic kidney disease. Int J Hematol 112, 115–117 (2020). https://doi.org/10.1007/s12185-020-02846-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-020-02846-5

Keywords

  • Dasatinib
  • Hemodialysis
  • Pharmacokinetics
  • CML
  • Cardiotoxicity