Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy

CHEN Juan; GUAN Yanping; SUN Liangzhong; LI Yilei; WEI Haixia; ZHOU Shouning; CHEN Yan; ZHENG Ping

doi:10.6039/j.issn.1001-0408.2024.01.12

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Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy

更新时间：2024-01-11

- Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy
- ZHONGGUO YAOFANG Vol. 35, Issue 1, Pages: 69-74(2024)
- 作者机构：
  
  1.南方医科大学南方医院临床药学中心，广州　510515
  2.中山大学药学院临床药理研究所，广州　510080
  3.南方医科大学南方医院儿科，广州　510515
  4.广州医科大学附属第一医院药学部，广州　510120
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.01.12
  CLC： R969.1
- Published：15 January 2024，
  
  Received：04 July 2023，
  
  Revised：20 November 2023，
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陈娟,管宴萍,孙良忠等.霉酚酸在原发性IgA肾病患儿中的群体药动学研究 ^Δ[J].中国药房,2024,35(01):69-74.

CHEN Juan,GUAN Yanping,SUN Liangzhong,et al.Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy[J].ZHONGGUO YAOFANG,2024,35(01):69-74.
陈娟,管宴萍,孙良忠等.霉酚酸在原发性IgA肾病患儿中的群体药动学研究 ^Δ[J].中国药房,2024,35(01):69-74. DOI： 10.6039/j.issn.1001-0408.2024.01.12.

CHEN Juan,GUAN Yanping,SUN Liangzhong,et al.Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy[J].ZHONGGUO YAOFANG,2024,35(01):69-74. DOI： 10.6039/j.issn.1001-0408.2024.01.12.

摘要

目的

建立霉酚酸酯的活性代谢产物霉酚酸（MPA）在原发性IgA肾病患儿中的群体药动学（PPK）模型，探究影响MPA药动学参数的因素，为临床个体化给药提供参考。

方法

回顾性收集使用霉酚酸酯的47名原发性IgA肾病患儿的636个药物浓度监测数据及相应临床资料，利用非线性混合效应模型进行PPK分析，采用逐步回归法进行协变量筛选，通过拟合优度图、重抽样自举法和可视化预测检验法评价模型。

结果

原发性IgA肾病患儿MPA体内药动学符合一级吸收和消除二房室模型（目标函数值为3 276.31）。协变量分析提示体重和白蛋白（ALB）水平为表观清除率和表观分布容积的显著影响因素。通过最终模型估计可得MPA最终模型PPK参数群体典型值：中央室分布容积为5.79 L，清除率为4.06 L/h，外周室分布容积为430.93 L，隔室间清除率为15.40 L/h，口服吸收速率常数为1.29 h

－1

。经验证，预测校正观测浓度点大部分位于预测校正模拟浓度的90%置信区间内，说明MPA最终模型具有良好的预测性。

结论

建立了原发性IgA肾病患儿口服霉酚酸酯后MPA的PPK模型，明确了体重及ALB水平是MPA代谢的显著影响因素。

Abstract

OBJECTIVE

To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy.

METHODS

Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model.

RESULTS

The pharmacokinetics of MPA in children with IgA nephropathy

in vivo

conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h

－1

. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance.

CONCLUSIONS

The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

关键词

IgA肾病霉酚酸儿童群体药动学

Keywords

mycophenolic acidchildrenpopulation pharmacokinetics

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