Te Lintelo Amber M, van Wier Lisa F, van der Doef Hubert P J, Kosterink Jos G W, Scheenstra René, van Leer Coretta C, Bourgonje Arno R, Touw Daan J, Mian Paola
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Eur J Drug Metab Pharmacokinet. 2025 Jun 17. doi: 10.1007/s13318-025-00954-3.
Epstein-Barr virus (EBV) is a common herpesvirus among pediatric liver transplant recipients, but it can have serious complications, such as post-transplant lymphoproliferative disease. EBV is hypothesized to influence tacrolimus concentrations by increasing inflammatory cytokines that regulate the expression of cytochrome-P-450 enzymes involved in tacrolimus pharmacokinetics. This study aims to examine the association between EBV serostatus and viral load, and tacrolimus trough concentrations corrected for the dose and recipient weight [weight-adjusted concentration-to-dose (C/D) ratios].
This retrospective study includes pediatric liver transplant recipients aged 0-18 years old, transplanted at the University Medical Center Groningen between January 2008 and September 2021. This study utilized two cohorts: a cross-sectional and a longitudinal study database.
The association between EBV serostatus and the tacrolimus pharmacokinetics was examined using 45 recipients from both cohorts. The effect of EBV viral load on tacrolimus pharmacokinetics was examined using the longitudinal study database, which included 25 EBV-positive recipients. No significant effect of EBV on the tacrolimus weight-adjusted C/D ratios was found, for either EBV serostatus (p = 0.85) or EBV viral load (p = 0.85).
This study suggests that the standard protocol of tacrolimus dosing does not seem to require adjustments due to changes in EBV serostatus or viral load.
爱泼斯坦-巴尔病毒（EBV）是小儿肝移植受者中常见的疱疹病毒，但它可能引发严重并发症，如移植后淋巴增殖性疾病。据推测，EBV通过增加炎症细胞因子来影响他克莫司浓度，这些炎症细胞因子可调节参与他克莫司药代动力学的细胞色素P-450酶的表达。本研究旨在探讨EBV血清学状态和病毒载量与经剂量和受者体重校正后的他克莫司谷浓度[体重校正浓度-剂量（C/D）比值]之间的关联。
这项回顾性研究纳入了2008年1月至2021年9月期间在格罗宁根大学医学中心接受肝移植的0至18岁小儿肝移植受者。本研究使用了两个队列：一个横断面研究数据库和一个纵向研究数据库。
使用两个队列中的45名受者研究了EBV血清学状态与他克莫司药代动力学之间的关联。使用纵向研究数据库（包括25名EBV阳性受者）研究了EBV病毒载量对他克莫司药代动力学的影响。未发现EBV血清学状态（p = 0.85）或EBV病毒载量（p = 0.85）对他克莫司体重校正C/D比值有显著影响。
本研究表明，由于EBV血清学状态或病毒载量的变化，他克莫司给药的标准方案似乎无需调整。
