NCT02011022

Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Lymphoblastic Malignancies

Pharmacokinetic Analysis of High Dose Methotrexate in Pediatric Acute Lymphoblastic Leukemia: Significant Impact Factors and Establishment of a Clinically Relevant Model

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 291 (actual)
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

\* The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling.

Detailed description

* Methotrexate (MTX) is one of the critical components for treating all forms of acute lymphoblastic leukemia (ALL), which is the most common pediatric cancer. Unfortunately, high dose MTX has several undesirable side effects and MTX toxicity vastly differs from patient to patient. * The pharmacokinetics of MTX were assessed with regards to the relevance of several different patient specific factors in 291 pediatric patients, who were administered with high dose of MTX. Population pharmacokinetics of MTX analysis was performed by using nonlinear mixed effects modeling. * The final model was validated using nonparametric bootstrap analysis. Body surface area (BSA), pre-hydration, baseline serum creatinine and 24 h creatinine clearance rate were statistically significant covariates for distributional volume (V) and renal clearance (CL). Herein, is the first report of analysis of the importance of a series of patient factors on pharmacokinetics of MTX by one-compartment model. Using these data, we have established an efficient population pharmacokinetic model for MTX, which can be used to predict safe clinical application of MTX especially in children with ALL.

Conditions

• Methotrexate Adverse Reaction

Interventions

Type	Name	Description
DRUG	3g MTX	The group of patients which are treated with 3g/m2 MTX, low risk ALL or NHL
DRUG	5g MTX	The group of patients which are treated with 5g/m2 MTX, they are high or middle risk ALL patients

Timeline

• Start date: 2009-05-01
• Primary completion: 2009-12-01
• Completion: 2010-02-01
• First posted: 2013-12-13
• Last updated: 2013-12-13

Locations

1 site across 1 country: China