In:
Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 1 ( 2018-02), p. 76-83
Abstract:
The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined according to age. Methods: The authors included a total of 106 cycles, corresponding to 33 patients (mean age: 9.8 years, range: 2–18 years) suffering from acute lymphoblastic leukemia, non-Hodgkin lymphoma and osteosarcoma and receiving high-dose MTX (HD-MTX). Plasma MTX, 7-OHMTX, and creatinine at T24 and T48 hours were measured. Results: Children older than 14 years had significantly higher MTX levels at T48 hours (1.25 versus 0.5 μmol/L, P 〈 0.05) and a higher MTX/7-OHMTX ratio (0.63 versus 0.20, P 〈 0.05) than children younger than 6 years. Plasma 7-OHMTX at T24 and T48 hours was positively correlated with serum creatinine and creatinine ratio at T24 and T48 hours. MTX levels provided a better specificity and sensitivity at both 24 and 48 hours than 7-OHMTX to predict delayed MTX elimination. A MTX threshold close to 0.83 μmol/L at T48 hours improved specificity from 58% to 82% and keeps sensitivity at 100%. The authors identified a cut-off at 65 μmol/L for MTX at T24 hours with a good sensitivity (75%) and specificity above 50%. Conclusions: These results confirm the concentration-dependent nephrotoxicity of 7-OHMTX. Children older than 14 years old had a higher MTX levels at 48 hours and a higher MTX/7-OHMTX ratio, suggesting a faster metabolism in younger children. This study identified a higher and more specific MTX threshold at T48 hours compared to those currently used, and a new threshold at T24 hours.
Type of Medium:
Online Resource
ISSN:
0163-4356
DOI:
10.1097/FTD.0000000000000445
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
2048919-5
SSG:
15,3
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