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.
Pediatr Blood Cancer. 2019 May;66(5):e27618. doi: 10.1002/pbc.27618. Epub 2019 Jan 24.
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.
我们旨在确定在接受高剂量甲氨蝶呤（HDMTX）治疗期间同时接受达沙替尼或伊马替尼治疗的患者与未接受酪氨酸激酶抑制剂（TKI）治疗的患者相比，甲氨蝶呤清除率是否较慢。同时接受达沙替尼和 HDMTX 治疗的 7 名患者的 MTX 清除率明显较慢（P=0.008），而未接受 TKI 治疗的 111 名患者的 MTX 清除率较慢（P=0.008）。在 HDMTX 输注期间接受 TKI 治疗的 2 名患者需要使用葡萄糖醛酸酶。体外研究表明，达沙替尼可显著抑制 SLCO1B1 表达细胞对甲氨蝶呤的摄取（P=0.009）。达沙替尼和 HDMTX 之间可能存在相互作用，由转运蛋白 SLCO1B1 介导，导致 MTX 清除延迟。
