Biotechnology in Health and Investigative Medicine Postgraduate Program, Gonçalo Moniz Institute, Oswaldo Cruz Foundation (Fiocruz), Salvador, Bahia, Brazil.
Clinical Biochemistry Laboratory, Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Bahia/UFBA, University Campus, Barão de Jeremoabo Street, Ondina, Salvador, Bahia, Brazil.
Curr Drug Res Rev. 2024;16(3):403-411. doi: 10.2174/0125899775266172231004074317.
Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy.
This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy.
Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL was considered therapeutic.
Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability.
The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.
急性排斥反应仍然是移植后最初几个月的主要并发症之一，可能会影响长期结果。他克莫司在实体器官移植中已被证明有效，通过应用药代动力学概念来监测它，以优化个体药物治疗。
本研究旨在评估甲基泼尼松龙脉冲治疗下疑似急性肾移植排斥反应患者的他克莫司药代动力学参数。
从前瞻性、单臂、单中心队列研究中选择 11 名接受他克莫司治疗的成年肾移植受者，他们尽管在使用甲基泼尼松龙脉冲治疗，但疑似发生急性排斥反应。在移植后三个月内对他们进行随访，使用化学发光磁免疫测定法测定他克莫司谷浓度，并通过 Monolix 2020R1 实现的非线性混合效应模型估计药代动力学参数。将他克莫司谷浓度范围 8 至 12ng.mL 定义为治疗范围。
6 名患者出现急性细胞排斥反应，其中 2 名患者同时存在抗体介导的排斥反应。8 名患者的他克莫司谷浓度低于参考范围。大多数患者表现出高个体内和药代动力学参数变异性的他克莫司浓度。
所获得的药代动力学参数有助于了解肾移植受者的他克莫司行为，有助于改善个体药物治疗并降低急性排斥反应发作的风险。
