Methotrexate-Induced Nephrotoxicity and Exposure Thresholds in Primary Central Nervous System Lymphoma: A Population PKPD Model
A new monitoring approach identifies which cancer patients are at high risk for kidney damage from chemotherapy before treatment starts, using readily available blood data.
A population PKPD model derived from 5,918 plasma samples of 743 PCNSL patients establishes quantitative MTX concentration thresholds for Grade ≥2 nephrotoxicity at 24/48/72 hours, enabling individualized therapeutic drug monitoring risk calibration. Hemoglobin emerged as the primary predictor of renal susceptibility, providing a clinically accessible covariate for pre-treatment risk stratification.
What the study was
- Study design
- Retrospective population pharmacokinetic/pharmacodynamic (PKPD) modeling
- Population
- Chinese adult PCNSL patients receiving high-dose methotrexate
- Sample size
- 743
- Category
- Diagnostics
- Maturity
- Validated
- Journal
- Clinical Pharmacology & Therapeutics
Why it surfaced
Largest PKPD model for MTX nephrotoxicity in PCNSL to date (N=743); provides actionable concentration thresholds complementing standard TDM practice. Near-term implementable for clinical pharmacology teams managing HD-MTX.
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