Sun Zhi-Hua, Zhao Yi-Chang, Li Jia-Kai, Peng Fenghua, Yu Feng, Zhang Bi-Kui, Yan Miao
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China.
Front Pharmacol. 2025 Jan 29;15:1502097. doi: 10.3389/fphar.2024.1502097. eCollection 2024.
The concurrent administration of tacrolimus and voriconazole in kidney transplant recipients can lead to drug interactions, potentially resulting in severe adverse reactions. This study aimed to establish a robust population pharmacokinetic model to explore the interaction between tacrolimus and voriconazole in greater depth.
Tacrolimus blood samples and laboratory data were prospectively collected from eligible patients enrolled between April 2023 and April 2024, following predefined inclusion and exclusion criteria. Using Phoenix (version 8.1), a pharmacokinetic prediction model was developed. Model performance was assessed using model fitting plots, bootstrap analysis, and visual predictive checks (VPC).
This study ultimately included 51 eligible patients, with a total of 281 blood samples collected. Analysis revealed a significant negative correlation between voriconazole concentration (Cvrc) and tacrolimus volume of clearance rate (CL), a significant positive correlation between platelets (PLT) and tacrolimus clearance (CL), and a significant negative correlation between blood cells (RBC) and tacrolimus clearance (CL).
This study successfully established a population pharmacokinetic model for renal transplant patients concurrently receiving tacrolimus and voriconazole. The model demonstrated good predictive performance and offers valuable insights to clinicians for optimizing tacrolimus dosing in this patient population.
肾移植受者同时使用他克莫司和伏立康唑可能导致药物相互作用，进而可能引发严重不良反应。本研究旨在建立一个稳健的群体药代动力学模型，以更深入地探讨他克莫司与伏立康唑之间的相互作用。
根据预先定义的纳入和排除标准，前瞻性收集2023年4月至2024年4月期间符合条件患者的他克莫司血样和实验室数据。使用Phoenix（8.1版）开发了药代动力学预测模型。通过模型拟合图、自抽样分析和可视化预测检查（VPC）评估模型性能。
本研究最终纳入51例符合条件的患者，共采集281份血样。分析显示伏立康唑浓度（Cvrc）与他克莫司清除率（CL）呈显著负相关，血小板（PLT）与他克莫司清除率（CL）呈显著正相关，血细胞（RBC）与他克莫司清除率（CL）呈显著负相关。
本研究成功建立了同时接受他克莫司和伏立康唑的肾移植患者群体药代动力学模型。该模型显示出良好的预测性能，为临床医生优化该患者群体的他克莫司给药提供了有价值的见解。
