Abstract:

Objective The published literature on population pharmacokinetic modeling of oral Tacrolimusfor 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 populationpharmacokinetic model of adult liver transplantation patients in our center.

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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。

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