Pharma / Biotech

Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib.


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Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib.

Pediatr Blood Cancer. 2019 Jan 24;:e27618

Authors: Ramsey LB, Mizuno T, Vinks AA, O’Brien MM

Abstract
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.

PMID: 30677213 [PubMed – as supplied by publisher]

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