期刊
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
卷 15, 期 1, 页码 105-117出版社
WILEY
DOI: 10.1111/cts.13125
关键词
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资金
- Hematology Oncology Pharmacy Association (HOPA) Foundation Research Grant Program
- National Institutes of Health Center for Translational Science Activities from the National Center for Advancing Translational Science (NCATS) [TL1 TR002380]
- National Center Institute from the National Institute of Allergy and Infectious Diseases [P30 CA015083, K23AI143882]
This study evaluated the pharmacokinetics of high-dose methotrexate (HDMTX) in adult lymphoma patients, finding that the cystatin C-based eGFR equation best predicted MTX clearance and highlighting the high interpatient variability in HDMTX pharmacokinetics.
High-dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single-center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7-hydroxy-MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine- or cystatin C-based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2-75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8-11.3) grams. Median clearance was similar across three dosing levels at 4.5-5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFR(cys) (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4-h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C-based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.
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