Department of Pharmacy, Peking University Third Hospital, Beijing, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Transplant Rev (Orlando). 2024 Dec;38(4):100878. doi: 10.1016/j.trre.2024.100878. Epub 2024 Sep 7.
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.
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.
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.
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.
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.
他克莫司是移植后免疫抑制方案的基石。尽管进行了常规监测，但药物谷浓度反映药物浓度波动的效果有限。患者内变异（IPV）作为一种新的监测标志物，用于预测临床结局。然而，理解影响 IPV 的因素并评估解决这些因素的干预措施仍然是一个谜，这在临床管理中构成了一个难题。
本系统评价旨在研究影响 IPV 的一系列因素，并评估策略干预的效果，从而为加强临床管理提供指导。
我们电子检索了 PubMed、Embase 和 Cochrane 图书馆数据库，以获取截至 2023 年 10 月研究影响 IPV 的因素和干预措施的研究。两名审查员独立筛选文献、提取数据并评估质量，使用 RevMan 5.4.1 软件进行荟萃分析。
共纳入 15 项随机对照试验（RCT）、34 项队列研究和 20 项自身对照研究。结果表明，CYP3A5 表达者、不依从患者、服用质子泵抑制剂或他汀类药物的患者和黑种人或非裔美国人患者的 IPV 显著更高，而服用延长释放制剂的患者的 IPV 较低。此外，药师的参与对改善 IPV 有积极影响。
影响 IPV 的因素包括基因型、制剂、依从性、药物组合和种族，每个因素的影响程度不同。确定这些因素对于制定有针对性的干预策略至关重要。虽然药师的参与有望改善 IPV，但需要进一步研究移动技术、提高依从性的教育措施和个性化剂量方案等干预措施。
