Exploratory associations of tacrolimus exposure and clinical outcomes after lung transplantation: A retrospective, single center experience.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY

European Journal of Clinical Pharmacology Pub Date : 2024-05-01 Epub Date: 2024-02-16 DOI:10.1007/s00228-024-03640-6

Wenwen Du, Xiaoxing Wang, Dan Zhang, Xianbo Zuo

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Abstract

Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation.

Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C₀) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C₀ cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C₀ and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality.

Results: The influence of CYP3A5*3 polymorphism was only significant for C₀ and IPV during the first 3 months. Low C₀ (< 8 ng/mL) at 3-12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046-6.953) and mortality (HR 2.531, 95% CI 1.368-4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336-4.839). Patients with Low C₀/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279-15.008) and survival (HR 6.179, 95% CI 2.598-14.698), surpassing the predictive power provided by C₀ or IPV alone.

Conclusion: A combination of Low C₀/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation.

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肺移植术后他克莫司暴露与临床结果的探索性关联：回顾性单中心经验

目的：本研究旨在探讨他克莫司（TAC）暴露对肺移植术后临床结果的潜在影响：这项回顾性观察研究共纳入了 228 例肺移植受者。在0-3个月、3-12个月和12-24个月的3个时间间隔内收集TAC谷值（C0）。采用变异系数计算患者内变异性（IPV）。对 CYP3A5*3 (rs776746) 进行了基因分型。根据 8 纳克/毫升的 C0 临界值和 30% 的 IPV 临界值，将患者进一步分为几组。采用 Cox 比例危险度回归模型探讨 C0 和 IPV 对相关结果的潜在影响，包括去供体特异性抗体（dnDSA）、慢性肺移植功能障碍（CLAD）和死亡率：CYP3A5*3多态性仅对前三个月的C0和IPV有显著影响。低 C0（0/高 IPV）组合对 dnDSA（HR 4.381，95% CI 1.279-15.008）和生存（HR 6.179，95% CI 2.598-14.698）的风险显著较高，超过了单独使用 C0 或 IPV 的预测能力：结论：在对肺移植后有不良临床结果风险的患者进行分类时，可考虑将低C0/高IPV结合起来。

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

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.