Renal Function and Plasma Methotrexate Concentrations Predict Toxicities in Adults Receiving High-Dose Methotrexate
Yunyun Yang, Xuebin Wang, Jing Tian, Zhuo Wang
Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, China (mainland)
Med Sci Monit 2018; 24:7719-7726
Methotrexate (MTX) is an effective drug for the treatment of adult malignancies, but toxicity remains a significant problem. Toxic reactions may occur when patients use high-dose MTX (HD-MTX), but the correlation between its toxicity and concentration in adults is controversial. The purpose of this study was to examine the relationship between MTX concentration and renal function, as well as to assess toxic reactions to MTX in Chinese adults with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL).
MATERIAL AND METHODS: This retrospective study enrolled 97 patients who had been diagnosed with ALL or NHL, and who were treated at the Hemopathology Department of Shanghai Changhai Hospital from January 2015 to June 2016.
RESULTS: Forty-one (27.5%) episodes of elimination delay were observed. We found negative correlations between creatinine clearance rate before MTX infusion and the plasma concentrations of MTX at 36 h after MTX infusion (P=0.005). The serum creatinine at 48 h and plasma concentrations of MTX at 48 h and72 h were significantly and positively correlated (both p=0.000). High blood concentration of MTX was positively associated with nephrotoxicity > grade 1 (P<0.01). Infection > grade 1 was more likely to occur if a patient had high MTX levels at 36 h,48 h, and 72 h (P<0.01).
CONCLUSIONS: Our results show that renal function is associated with MTX concentration, and high MTX concentration can predict the occurrence of renal toxicity and infection related to MTX.
Keywords: Creatinine, Drug-Related Side Effects and Adverse Reactions, Methotrexate