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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

2025 Vol.26 No.9 P.897-914

A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants

Shuang LIU, Hongsheng CHEN, Zaiwei SONG, Qi GUO, Xianglin ZHANG, Bingyi SHI, Suodi ZHAI, Lingli ZHANG, Liyan MIAO, Liyan CUI, Xiao CHEN, Yalin DONG, Weihong GE, Xiaofei HOU, Ling JIANG, Long LIU, Lihong LIU, Maobai LIU, Tao LIN, Xiaoyang LU, Lulin MA, Changxi WANG, Jianyong WU, Wei WANG, Zhuo WANG, Ting XU, Wujun XUE, Bikui ZHANG, Guanren ZHAO, Jun ZHANG, Limei ZHAO, Qingchun ZHAO, Xiaojian ZHANG, Yi ZHANG, Yu ZHANG, Rongsheng ZHAO

Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China; Kidney Transplant Quality Control Center of National Health Commission, The 8th Medical Center of Chinese PLA General Hospital,, Beijing 100000, China; Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou 215006, China; Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100191, China; Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 8Department of Pharmacy, The First Affiliated Hospital of Xian Jiaotong University, Xian 710061, China; Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China; Department of Urology, Peking University Third Hospital, Beijing 100191, China; 1Department of Pharmacy, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, China; Department of Urology, General Hospital of Northern Theater Command, Shenyang 110003, China; Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, China; Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China; 5Department of Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 7Kidney Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; 8Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; 9Department of Pharmacy, The First Hospital Affiliated to Army Medical University, Shanghai 200433, China; 0Department of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China; Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xian Jiaotong University, Xian 710061, China; Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, China; Department of Pharmacy, The 8th Medical Center of Chinese PLA General Hospital, Beijing 100000, China; Department of Clinical Pharmacy, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China; Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China; 6Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110003, China; 7Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Department of Pharmacy, Tianjin First Central Hospital, Tianjin 300192, China; Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

zhaorongsheng@bjmu.edu.cn

Abstract: Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍–‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.

Key words: Guideline; Mycophenolic acid (MPA); Therapeutic drug monitoring (TDM); Grading of Recommendations Assessment, Development, and Evaluation (GRADE); Solid organ transplant

Chinese Summary  <1> 实体器官移植霉酚酸治疗药物监测循证指南

刘爽1， 陈鸿圣1， 宋再伟1， 郭琦1， 张相林2， 石炳毅3， 翟所迪1， 张伶俐4， 缪丽燕5， 崔丽艳6， 陈孝7， 董亚琳8， 葛卫红9， 侯小飞10， 姜玲11， 刘龙12， 刘丽宏2， 刘茂柏13， 林涛14， 卢晓阳15， 马潞林10， 王长希16， 吴建永17， 王玮18， 王卓19， 徐珽20， 薛武军21， 张毕奎22， 赵冠人23， 张峻24， 肇丽梅25， 赵庆春26， 张晓坚27， 张弋28， 张玉29， 赵荣生1
1北京大学第三医院药学部， 中国北京市， 100191
2中日友好医院药学部， 中国北京市， 100029
3国家卫生健康委员会肾脏移植质量控制中心， 中国人民解放军总医院第八医学中心， 中国北京市， 100000
4四川大学华西第二医院药学部， 中国成都市， 610041
5苏州大学第一附属医院药学部， 中国苏州市， 215006
6北京大学第三医院检验科， 中国北京市， 100191
7中山大学第一附属医院药学部， 中国广州市， 510080
8西安交通大学第一附属医院药学部， 中国西安市， 710061
9南京鼓楼医院药学部， 中国南京市， 210008
10北京大学第三医院泌尿外科， 中国北京市， 100191
11安徽省立医院药学部， 中国合肥市， 230001
12中国人民解放军北部战区总医院泌尿外科， 中国沈阳市， 110003
13福建医科大学附属协和医院药学部， 中国福州市， 350001
14四川大学华西医院泌尿外科， 中国成都市， 610041
15浙江大学医学院第一附属医院药学部， 中国杭州市， 310003
16中山大学第一附属医院器官移植中心， 中国广州市， 510080
17浙江大学医学院第一附属医院肾脏病中心， 中国杭州市， 310003
18首都医科大学附属北京朝阳医院泌尿外科， 中国北京市， 100020
19海军军医大学第一附属医院药学部， 中国上海市， 200433
20四川大学华西医院药剂科， 中国成都市， 610041
21西安交通大学第一附属医院肾脏移植科， 中国西安市， 710061
22中南大学湘雅二医院药剂科， 中国长沙市， 410011
23中国人民解放军总医院第八医学中心药剂科， 中国北京市， 100000
24昆明医科大学第一附属医院临床药学科， 中国昆明市， 650032
25中国医科大学附属盛京医院药学部 ，中国沈阳市， 110004
26中国人民解放军北部战区总医院药学部， 中国沈阳市， 110003
27郑州大学第一附属医院药学部， 中国郑州市， 450052
28天津市第一中心医院药学部， 中国天津市， 300192
29华中科技大学同济医学院附属协和医院药学部， 中国武汉市， 430022
摘要：霉酚酸（mycophenolic acid，MPA）类药物是实体器官移植维持期治疗中常用的免疫抑制剂，具有重要的临床意义。由于在体内代谢存在显著的个体间及个体内差异，开展治疗药物监测（therapeutic drug monitoring，TDM）有助于MPA的个体化合理应用，充分发挥其免疫抑制效应。然而，目前国内外实体器官移植的权威指南尚未提供MPA TDM的相关循证建议。本研究旨在基于循证方法制定MPA TDM指南，为临床合理应用MPA类药物提供指导。通过采用美国国家医学院（IOM）最新指南定义，并基于世界卫生组织（WHO）指南制定基本原则和方法，本研究制定指南计划书并在国际实践指南注册平台进行注册（注册号为IPGRP-2020CN099）。经德尔菲法确定指南纳入的临床问题及结局指标，开展系统评价制定指南临床问题的循证证据，结合GRADE证据质量评价、专家意见及患者意愿与价值观，由外审专家评审后，最终形成指南推荐意见。MPA TDM循证指南共形成4个部分16条推荐意见，涉及目标人群、监测指标、检测方法、剂量方案及浓度影响因素。指南进一步明确了MPA TDM高危人群定义、MPA采样时间、监测指标曲线下面积（AUC）与谷浓度（C0）比较、目标浓度范围、监测频率及检测方法比较。此外，指南还基于不同制剂比较、初始剂量方案确定、特殊人群个体化方案调整、体重因素、基因多态性及药物相互作用等方面，对MPA类药物的合理应用提供了循证建议。开展MPA TDM时，建议结合患者个体化特征进行综合评估，并根据患者的药物暴露和临床反应进行剂量调整。基于最新循证证据、专家经验及患者意愿制定的MPA TDM指南，为实体器官移植受者接受MPA类药物治疗提供了更为全面和详细的指导，有助于推动MPA TDM在临床实践中的规范化和标准化，从而提高移植受者的治疗效果和安全性。

关键词组：循证指南；霉酚酸（MPA）类药物；治疗药物监测（TDM）；GRADE；实体器官移植


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DOI:

10.1631/jzus.B2400069

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2025-06-23

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