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Delayed methotrexate clearance in patients with acute lymphoblastic leukemia concurrently receiving dasatinib
Authors:Laura B Ramsey  Tomoyuki Mizuno  Alexander A Vinks  Maureen M O'Brien
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.
Keywords:acute lymphoblastic leukemia  dasatinib  glucarpidase  imatinib  methotrexate  pharmacokinetics
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