期刊
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
卷 14, 期 1, 页码 343-353出版社
WILEY
DOI: 10.1111/cts.12879
关键词
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资金
- National Institutes of Health (NIH) National Institute of General Medical Sciences [GM007569, GM099924, GM124109, GM109145, GM131770]
- NIH National Cancer Institute [CA090625]
- First Nonprofit Foundation/Lily's Garden Research Fund (Vanderbilt University Medical Center)
- Alex's Lemonade Stand Foundation [17-00375]
- Rally Foundation
- Hyundai Hope on Wheels
- Burroughs Wellcome Fund [IRSA 1015006]
- National Center for Advancing Translational Sciences (CTSA award) [UL1 TR002243]
High-dose methotrexate is a critical treatment component for hematologic malignancies in children and young adults. This study found that patient weight and SLCO1B1 genotype significantly influence MTX clearance variability, highlighting the importance of considering these factors in personalized dosing of high-dose MTX.
High-dose (HD) methotrexate (MTX) is a critical component of treatment for hematologic malignancies in children and young adults. Therapeutic drug monitoring is necessary due to substantial interindividual variation in MTX clearance. Common function-altering polymorphisms inSLCO1B1(encodes OATP1B1, which transports MTX) may contribute to clearance variability. We performed pharmacokinetic modeling using data for 106 children and young adults treated with HD MTX for hematologic malignancies; of 396 total courses of HD MTX, 360 consisted of 5 g/m(2)over 24 hours. We evaluated the contribution of clinical covariates andSLCO1B1genotype (388A>G and 521T>C) to MTX clearance variability. Of the clinical covariates studied, patient weight improved the pharmacokinetic model most significantly (P < 0.001). The addition of theSLCO1B1variants individually further improved the model (P < 0.05 for each). An interaction between these variants was suggested when both were included (P = 0.017).SLCO1B1genotype should be considered in efforts to personalize HD MTX dosing.
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