Factors and interventions affecting tacrolimus intrapatient variability: A systematic review and meta-analysis

IF 3.6 2区医学 Q2 IMMUNOLOGY

Transplantation Reviews Pub Date : 2024-09-07 DOI:10.1016/j.trre.2024.100878

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引用次数: 0

Abstract

Backgrounds

Tacrolimus is a cornerstone of posttransplantation immunosuppressive regimens. Despite routine monitoring, the efficacy of its trough concentrations in reflecting drug concentration fluctuations is limited. Intrapatient variability (IPV) emerges as a novel monitoring marker for predicting clinical outcomes. However, understanding the factors affecting IPV and assessing interventions to address it remain enigmatic, posing a conundrum in clinical management.

Objectives

This systematic review aimed to investigate a spectrum of factors affecting IPV and assess the effect of strategic interventions, thereby charting a course for enhanced clinical stewardship.

Methods

We electronically searched of PubMed, Embase, and the Cochrane Library databases for studies investigating factors and interventions affecting IPV up to October 2023. Two reviewers independently screened literature, extracted data, and assessed quality, using RevMan 5.4.1 software for meta-analysis.

Results

A total of 15 randomized controlled trials (RCTs), 34 cohort studies, and 20 self-controlled studies were included. The results indicated that IPV was significantly higher in cytochrome P450 3A5 (CYP3A5) expressers, nonadherent patients, patients taking proton pump inhibitors or statins, and Black or African American recipients, whereas recipients consuming extended-release formulation exhibited lower IPV. Additionally, the participation of pharmacists had a positive effect on improving IPV.

Conclusions

Factors affecting IPV encompassed genotype, formulation, adherence, drug combinations, and ethnicity, with each factor exerting varying degrees of effect. Identifying these factors was crucial for developing targeted intervention strategies. While the participation of pharmacists held a promise in improving IPV, further investigation of interventions such as mobile technology, educational measures to enhance adherence, and personalized dosing regimens was warranted.

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影响他克莫司患者间变异性的因素和干预措施：系统回顾和荟萃分析

背景他克莫司是移植后免疫抑制疗法的基石。尽管进行了常规监测，但其谷浓度在反映药物浓度波动方面的效果有限。患者体内变异性（IPV）成为预测临床结果的新型监测指标。本系统综述旨在研究影响 IPV 的一系列因素，并评估战略性干预措施的效果，从而为加强临床管理指明方向。方法我们以电子方式检索了 PubMed、Embase 和 Cochrane Library 数据库中截至 2023 年 10 月有关影响 IPV 的因素和干预措施的研究。结果共纳入 15 项随机对照试验 (RCT)、34 项队列研究和 20 项自我对照研究。结果表明，细胞色素 P450 3A5 (CYP3A5) 表达者、不依从性患者、服用质子泵抑制剂或他汀类药物的患者以及黑人或非裔美国人受者的 IPV 明显较高，而服用缓释制剂的受者的 IPV 较低。结论影响 IPV 的因素包括基因型、制剂、依从性、药物组合和种族，每个因素都会产生不同程度的影响。确定这些因素对于制定有针对性的干预策略至关重要。虽然药剂师的参与有望改善 IPV，但仍有必要进一步研究移动技术、提高依从性的教育措施和个性化给药方案等干预措施。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplantation Reviews IMMUNOLOGY-TRANSPLANTATION

CiteScore

7.50

自引率

2.50%

发文量

审稿时长

29 days

期刊介绍： Transplantation Reviews contains state-of-the-art review articles on both clinical and experimental transplantation. The journal features invited articles by authorities in immunology, transplantation medicine and surgery.