Page 79 - 《中国药房》2024年1期

·药物与临床·

霉酚酸在原发性IgA肾病患儿中的群体药动学研究
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陈 娟 ，管宴萍 ，孙良忠 ，李亦蕾 ，魏海霞 ，周守宁 ，陈 艳 ，郑 萍 （1.南方医科大学南方医院临床药学
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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）
中图分类号 R969.1 文献标志码 A 文章编号 1001-0408（2024）01-0069-06
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 。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
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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。
关键词 IgA肾病；霉酚酸；儿童；群体药动学

Population pharmacokinetics of mycophenolic acid in pediatric patients with primary IgA nephropathy
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CHEN Juan ，GUAN Yanping ，SUN Liangzhong ，LI Yilei ，WEI Haixia ，ZHOU Shouning ，CHEN Yan ，
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ZHENG Ping（1. Clinical Pharmacy Center， Nanfang Hospital of Southern Medical University， Guangzhou
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510515， China；2. Institute of Clinical Pharmacology， School of Pharmacy， Sun Yat-sen University， Guangzhou
510080， China；3. Dept. of Pediatrics， Nanfang Hospital of Southern Medical University， Guangzhou 510515，
China；4. Dept. of Pharmacy，the First Affiliated Hospital of Guangzhou Medical University，Guangzhou 510120，
China）
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 .
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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
Δ 基金项目 广东省医院药学研究基金项目（No.2023A16）
＊第一作者 主管药师。研究方向：药代动力学与药物基因组学。 metabolism.
E-mail：juanke526@163.com KEYWORDS IgA nephropathy； mycophenolic acid； children；
# 通信作者 主任药师，硕士。研究方向：医院药学、临床药学。 population pharmacokinetics
E-mail：zpm321@126.com

中国药房 2024年第35卷第1期 China Pharmacy 2024 Vol. 35 No. 1 · 69 ·