Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib.
Division of Research in Patient Services, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
- Published Article
Pediatric Blood & Cancer
Wiley (John Wiley & Sons)
- Publication Date
May 01, 2019
We aimed to determine whether patients receiving dasatinib or imatinib concurrently with high-dose methotrexate (HDMTX) had slower methotrexate clearance than patients not receiving a tyrosine kinase inhibitor (TKI) during the HDMTX infusion. Patients concurrently receiving dasatinib and HDMTX (N = 7) had significantly slower MTX clearance (P = 0.008) than patients not receiving a TKI (N = 111). Two patients receiving a TKI during a HDMTX infusion required glucarpidase. In vitro studies showed that dasatinib significantly inhibited methotrexate uptake by SLCO1B1-expressing cells (P = 0.009). There may be an interaction between dasatinib and HDMTX, mediated by the transporter SLCO1B1, that causes a delay in MTX clearance. © 2019 Wiley Periodicals, Inc.
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This record was last updated on 06/23/2020 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/30677213