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Renal Function and Plasma Methotrexate Concentrations Predict Toxicities in Adults Receiving High-Dose Methotrexate
Yunyun Yang1, Xuebin Wang1, Jing Tian1
1Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland).
Summary
High-dose methotrexate (MTX) concentration correlates with renal toxicity and infection risk in adult acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) patients. Monitoring MTX levels is crucial for managing toxicity.
Area of Science:
- Oncology
- Pharmacology
- Nephrology
Background:
- Methotrexate (MTX) is a vital chemotherapeutic agent for adult malignancies.
- High-dose MTX (HD-MTX) is associated with significant toxicity, but its concentration-toxicity relationship in adults is debated.
- Understanding MTX pharmacokinetics is critical for optimizing treatment and minimizing adverse events.
Purpose of the Study:
- To investigate the association between MTX concentration and renal function in Chinese adults.
- To evaluate the correlation between MTX levels and toxic reactions, including nephrotoxicity and infection.
- To assess the predictive value of MTX concentration for adverse events in patients with ALL and NHL.
Main Methods:
- Retrospective study of 97 adult patients diagnosed with ALL or NHL.
- Patients treated with HD-MTX at Shanghai Changhai Hospital between January 2015 and June 2016.
- Analysis of plasma MTX concentrations, creatinine clearance, serum creatinine, and occurrence of toxic reactions.
Main Results:
- 27.5% of treatment episodes showed delayed MTX elimination.
- Negative correlation found between pre-infusion creatinine clearance and MTX levels at 36 hours (P=0.005).
- Positive correlations observed between serum creatinine at 48 hours and MTX levels at 48/72 hours (p=0.000).
- High MTX blood concentration significantly associated with nephrotoxicity > grade 1 (P<0.01).
- Higher MTX levels at 36, 48, and 72 hours increased the likelihood of infection > grade 1 (P<0.01).
Conclusions:
- Renal function significantly influences MTX concentration in adult patients.
- Elevated MTX concentrations are predictive of MTX-related renal toxicity and infection.
- Therapeutic drug monitoring of MTX is essential for managing toxicity in oncology patients.
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