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

VernacularTitle:甲氨蝶呤在多种儿童肿瘤患者中的群体药代动力学研究
Author: Yan GONG ¹ ; Weijing GONG ¹ ; Jiaxin LI ¹ ; Yanjie QIN ¹ ; Li LUO ¹
Author Information

1. 华中科技大学同济医学院附属协和医院药学部,武汉 430022,湖北;湖北省重大疾病精准用药临床医学中心,武汉 430022,湖北
Publication Type:Journal Article
Keywords: methotrexate; pediatric malignan-cies; population pharmacokinetics; genetic poly-morphism
From: Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(1):70-77
CountryChina
Language:Chinese
Abstract: AIM:To establish a population phar-macokinetic(PPK)model of high-dose methotrex-ate in pediatric patients with diverse malignancies.METHODS:The PPK model of methotrexate was de-veloped using non-linear mixed-effects model;body surface area(BSA)was incorporated by allo-metric size modelling.RESULTS:A two-compart-ment linear model best fitted the concentration da-ta,typical values for clearance(CL)and central compartment distribution volume(Vd)were re-vealed 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.CON-CLUSION:Age,BSA,SCr and genotypes of ABCC2 rs717620 and ABCC4 rs2274407 were identified to be significantly affecting the clearance.