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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2025, Vol. 30 ›› Issue (1): 70-77.doi: 10.12092/j.issn.1009-2501.2025.01.008

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Population pharmacokinetics of high-dose methotrexate in pediatric patients with diverse malignancies

GONG Yan1,2, GONG Weijing1,2, LI Jiaxin1,2, QIN Yanjie1,2, LUO Li1,2   

  1. 1 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China; 2 Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan 430022, Hubei, China
  • Received:2024-04-11 Revised:2024-05-17 Online:2025-01-26 Published:2025-01-02

Abstract:

AIM: To establish a population pharmacokinetic (PPK) model of high-dose methotrexate in pediatric patients with diverse malignancies. METHODS: The PPK model of methotrexate was developed using non-linear mixed-effects model; body surface area (BSA) was incorporated by allometric size modelling. RESULTS: A two-compartment linear model best fitted the concentration data, typical values for clearance (CL) and central compartment distribution volume (Vd) were revealed to be 4.51 L/(h·1.73 m2) and 15.47 L/1.73 m2, respectively. Age, BSA, serum creatinine (SCr) and genotypes of ABCC2 rs717620 and ABCC4 rs2274407 were retained in the final model. CONCLUSION: Age, BSA, SCr and genotypes of ABCC2 rs717620 and ABCC4 rs2274407 were identified to be significantly affecting the clearance. 

Key words: methotrexate, pediatric malignancies, population pharmacokinetics, genetic polymorphism

CLC Number: