成人原位肝移植术后早期他克莫司个体化给药研究  

Personalized medicine of Tacrolimus in early postoperative phase in adult orthotopic liver transplantation

作　　者：邵佳[1] 陈凡[1] 马楠[1] 孙超[1] 魏金霞 闫美玲[1] 付鹏[1] 张瑞霞[1] 秦寅鹏 张弋[1] Shao Jia;Chen Fan;Ma Nan;Sun Chao;Wei Jinxia;Yan Meiling;Fu Peng;Zhang Ruixia;Qin Yinpeng;Zhang Yi(Department of Pharmacy,Tianjin First Central Hospital,Tianjin 300192,China;College of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津市第一中心医院药学部,天津300192 [2]天津中医药大学中药学院,天津301617

出　　处：《实用器官移植电子杂志》2020年第1期22-26,共5页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：国家自然科学基金项目(81803356和81703690);天津市第一中心医院科技基金(院CM201806);北京医卫健康公益基金会医学科学研究基金资助项目(YWJKJJHKYJJ-B16244);天津市自然科学基金项目(19JCQNJC12200);武警后勤学院博士启动基金项目(WHB201711)。

摘　　要：目的检索目前已发表的基于CYP3A5基因型成人肝移植口服他克莫司群体药动学建模文献,对自建模型和已发表模型进行拟合,筛选出适合本中心的群体药动学模型,用于患者初始剂量个体化给药。方法通过检索PubMed、Scopus和Web of Science三种数据库筛选出相关模型,使用本中心数据,采用正态分布预测分布误差法(normalised prediction distribution errors,NPDE)进行模型验证。结果收集到本单位进行肝移植手术的成人患者40例,检索到涉及供-受者CYP3A5基因型建模的一房室模型1个,二房室模型1个,自建二房室模型1个。经NPDE检验,采用自建模型进行模拟个体化给药,供-受者均为CYP3A5*1非携带者的达稳态推荐剂量范围为1.48~1.93 mg,供-受者任意一方为CYP3A5*1携带者达稳态推荐剂量为2.1~2.35 mg,供-受者均为CYP3A5*1携带者达稳态推荐剂量为2.7~2.9 mg。结论供-受者CYP3A5*1基因型需纳入模型用于患者个体化给药,未来采用此模型进行前瞻性研究,逐步完善本中心的成人肝移植患者的他克莫司群体药动学模型。Objective The published literature on population pharmacokinetic modeling of oral Tacrolimus for adult liver transplantation based on CYP3A5 genotype was searched,and the self-built model and published model were fitted to select the appropriate population pharmacokinetic model for the initial measurement and individualized treatment of patients.Methods The relevant models were screened out by searching PubMed,Scopus and Web of Science.The data were validated by normalized prediction distribution errors(NPDE).Results A total number of 40 adult patients with liver transplantation were collected in our center.One one-compartment model,one two-compartment model were retrieved,and one two-compartment self-built model was developed.NPDE showed that the recommended dose for both donors and recipients is 1.48~1.93 mg for non-carriers of CYP3A5*1,2.1~2.35 mg for either donors or recipients who carry CYP3A5*1,and 2.7~2.9 mg for both donors and recipients who carry CYP3A5*1.Conclusion Donor-recipient CYP3A5*1 genotypes should be included in the model for personalized medicine,and prospective studies should be carried out to gradually improve the Tacrolimus population pharmacokinetic model of adult liver transplantation patients in our center.

关 键 词：肝移植 成人 他克莫司 CYP3A5 

分 类 号：R657.3[医药卫生—外科学]