越南肾移植患者 CYP3A5*3 和他克莫司低浓度的药物基因组学分析

Thi Van Anh Nguyen, Ba Hai Le, Minh Thanh Nguyen, Viet Thang Le, Viet Tien Tran, Dinh Tuan Le, Duong Anh Minh Vu, Quy Kien Truong, Trong Hieu Le, Huong Thi Lien Nguyen
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引用次数: 0

摘要

目的:CYP3A5 多态性与肾移植患者他克莫司(Tac)药代动力学的变化有关。我们的研究旨在通过为患者选择合适的他克莫司群体药代动力学模型,量化 CYP3A5 基因型如何影响越南门诊患者的他克莫司谷浓度(C0):外部数据集来自103军医院治疗的54名成年肾移植受者的前瞻性数据。从 PubMed 和 Scopus 数据库中系统地筛选了所有已发表的 Tac 群体药代动力学模型,并根据我们患者的现有特征进行了筛选。使用平均绝对预测误差(MAPE)、平均预测误差和拟合优度图来确定合适的模型,以找到确定 CYP3A5 基因型对越南患者药代动力学数据影响的公式:Zhu 等人的模型具有良好的预测能力,MAPE 为 19.29%。CYP3A5 基因型对他克莫司清除率的影响用以下公式表示:.模拟结果显示,不表达 CYP3A5 的患者 Tac C0 明显更高(p< 0.001):结论:将 CYP3A5 表型纳入 Zhu 的结构模型,大大提高了我们预测越南人群他克莫司谷值水平的能力。该研究结果强调了 CYP3A5 表型在优化他克浓度预测中的重要作用,为协助医疗从业人员的临床决策提供了一条有前途的途径,并最终提高了患者的治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacogenomic Analysis of CYP3A5*3 and Tacrolimus Trough Concentrations in Vietnamese Renal Transplant Outcomes
Purpose: CYP3A5 polymorphisms have been associated with variations in the pharmacokinetics of tacrolimus (Tac) in kidney transplant patients. Our study aims to quantify how the CYP3A5 genotype influences tacrolimus trough concentrations (C0) in a Vietnamese outpatient population by selecting an appropriate population pharmacokinetic model of Tac for our patients.
Patients and Methods: The external dataset was obtained prospectively from 54 data of adult kidney transplant recipients treated at the 103 Military Hospital. All published Tac population pharmacokinetic models were systematically screened from PubMed and Scopus databases and were selected based on our patient’s available characteristics. Mean absolute prediction error (MAPE), mean prediction error, and goodness-of-fit plots were used to identify the appropriate model for finding the formula that identifies the influence of CYP3A5 genotype on the pharmacokinetic data of Vietnamese patients.
Results: The model of Zhu et al had a good predictive ability with MAPE of 19.29%. The influence of CYP3A5 genotype on tacrolimus clearance was expressed by the following formulas: . The simulation result showed that Tac C0 was significantly higher in patients not expressing CYP3A5 (p< 0.001).
Conclusion: The incorporation of the CYP3A5 phenotype into Zhu’s structural model has significantly enhanced our ability to predict Tacrolimus trough levels in the Vietnamese population. This study’s results underscore the valuable role of CYP3A5 phenotype in optimizing the forecast of Tac concentrations, offering a promising avenue to assist health-care practitioners in their clinical decision-making and ultimately advance patient care outcomes.

Keywords: tacrolimus, population pharmacokinetic, CYP3A5, Vietnam
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