地中海贫血造血干细胞移植术后患儿霉酚酸稳态谷浓度影响因素分析

Analysis of factors influencing mycophenolic acidsteady-state trough concentrations values in children with thalassemia after hematopoietic stem cell transplantation

目的:探讨地中海贫血造血干细胞移植(hematopoietic stem cell transplantation transplantation, HSCT)儿童患者霉酚酸(mycophenolic acid, MPA)稳态谷浓度的影响因素,为HSCT患儿MPA给药方案优化及临床应用提供参考。方法:前瞻性收集广西医科大学第一附属医院2022年10月至2023年4月使用吗替麦考酚酯(mycophenolate mofetil, MMF)并监测血药浓度的HSCT儿童患者病例信息及相关临床资料。采用多元回归分析考察MPA稳态谷浓度与协变量(年龄、性别、体质量、血常规、肝肾功能、合并用药等)的相关性,同时统计患儿用药期间发生药品不良反应(adverse drug reactions, ADR)信息。结果:共纳入36名患儿,161例次MPA稳态谷浓度,谷浓度中位数为0.531(0.233,1.038) mg·L^(-1)。尿素、性别是MPA稳态谷浓度的独立影响因素(P<0.05)。患儿服药后时间浓度折线图提示:HSCT患儿缺少肠肝循环,故MPA体内暴露量低。患儿用药后不良反应发生率为86.1%,主要涉及消化系统及感染。结论:HSCT儿童患者MPA稳态谷浓度达标率较低,尿素、性别、缺乏肠肝循环是影响MPA稳态谷浓度的主要因素;有必要进行药物浓度监测来优化HSCT儿童患者MMF给药方案。

OBJECTIVE To explore the factors influencing mycophenolic acid steady-state trough concentrations in pediatric patients with thalassemia undergoing HSCT,and to provide reference for mycophenolic acid dosing regimen optimization and clinical application.METHODS Information of pediatric patients who used mycophenolate mofetil and monitored blood concentrations from October 2022 to April 2023in The First Affiliated Hospital of Guangxi Medical University and related clinical data were collected;multiple regression analysis was used to examine the independent factors influencing mycophenolic acid steady-state trough concentrations,and information on the occurrence of adverse drug reaction(ADR)in children was recorded.RESULTS A total of 36 children with 161 cases of mycophenolic acid steady-state trough concentrations were included,The median trough concentration of mycophenolic acid was:0.531(0.233,1.038)mg·L^(-1).UREA and gender were independent influencing factors for steady-state trough concentration of mycophenolic acid(P<0.05);the concentration-time curves of every patient after drug administration suggested that the HSCT children lacked hepatic and intestinal circulation,so the exposure of mycophenolic acid in the body was low;The incidence of adverse reactions after drug administration in children was 86.1%,mainly related to the digestive system and infections.CONCLUSION The standardized rate of MPA steady-state trough concentration in children with HSCT is relatively low,and urea,gender,and lack of enterohepatic circulation are the main reasons that affect MPA steady-state trough concentration;It is necessary to conduct drug concentration monitoring to optimize the MMF dosing regimen for HSCT pediatric patients.