MTXPK.org Model Now Calibrated for Diverse Populations
Research By: Zachary Taylor, PhD, MS | Laura Ramsey, PhD
Post Date: August 3, 2023 | Publish Date: Aug. 3, 2023
Translational and Clinical Pharmacology | Top Scientific Achievement
A pharmacokinetics web tool designed to support optimal use of glucarpidase following the administration of high-dose methotrexate has been refined to apply to a wider range of patient populations thanks to research led by experts at Cincinnati Children’s.
The tool, MTXPX.org, was launched in 2019 but was tested primarily using data from a Nordic population of pediatric patients with acute lymphoblastic leukemia. This study describes HDMTX pharmacokinetics in a diverse patient cohort and identifies meaningful variability factors that improve the model’s performance.
The tool is important because high-dose methotrexate is a critical component of many cancer chemotherapy regimens. However, some patients experience delayed methotrexate elimination, increasing their risk for severe nephrotoxicity and death. Some patients can benefit from receiving glucarpidase to reduce this risk, but understanding when to use the drug has proven to be challenging.
The study, led by first author Zachary Taylor and corresponding author Laura Ramsey, provides a model, based on 7506 administrations of HDMTX to 1668 patients with conditions including acute lymphoblastic leukemia, osteosarcoma, and non-Hodgkin lymphoma. The findings offer adjusted parameters for severe hypoalbuminemia, short infusion duration, pleural effusion, and the presence of Down syndrome. The study also notes variations based on time of day for HDMTX administration.
“In addition to body surface area and serum creatinine, these new variables will improve the model’s performance and increase the generalizability of MTXPK.org now that it can describe more diverse patient data,” the co-authors say.
Cincinnati Children’s co-authors also included Ethan Poweleit, Sarah Board, Nick Ambrosino, and Maureen O’Brien. Collaborating institutions included Children’s Healthcare of Atlanta and Texas Children’s Hospital.
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| Original title: | Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org |
| Published in: | Clinical Translational Science |
| Publish date: | Aug. 3, 2023 |
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The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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