van Gelder Teun, Gelinck Armin, Meziyerh Soufian, de Vries Aiko P J, Moes Dirk Jan A R
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden Transplant Center, Leiden University Medical Center, Leiden, The Netherlands.
Br J Clin Pharmacol. 2025 Jun;91(6):1600-1606. doi: 10.1111/bcp.16098. Epub 2024 Jun 6.
Measurement of pre-dose tacrolimus concentrations, also referred to as trough concentrations or C0 (in this paper the term C0 will be used), is the most frequently used parameter for therapeutic drug monitoring in patients after solid organ transplantation. C0 is relatively easy to obtain, and can be combined with other lab tests. C0 monitoring is convenient for patient and hospital staff. Adjusting the dose based on C0 assumes that the C0 has a good correlation with the overall exposure to the drug, as reflected in the area under concentration-time curve (AUC). However, C0 may not be the panacea it is suggested to be, and there are patients who may benefit from additional measurements to more precisely assess drug exposure. Especially in patients with a low C0/dose ratio, the peak tacrolimus concentrations after oral administration may be unexpectedly high, resulting in toxicity and (as has been shown already) in poor long-term graft survival. At the other extreme, patients who only need a very low dose to reach target C0 may have a low peak and also a low AUC and may be underexposed. In this paper, the limitations of C0 will be discussed, and the type of studies needed to provide the evidence for implementation of more sophisticated therapeutic drug monitoring. The paper focuses on treatment of adult kidney transplant recipients.
测量给药前他克莫司浓度（也称为谷浓度或C0，本文将使用术语C0）是实体器官移植患者治疗药物监测中最常用的参数。C0相对容易获得，并且可以与其他实验室检查相结合。C0监测对患者和医院工作人员来说都很方便。基于C0调整剂量假定C0与药物的总体暴露量（以浓度-时间曲线下面积[AUC]表示）具有良好的相关性。然而，C0可能并非像人们认为的那样是万灵药，有些患者可能会从额外的测量中受益，以便更精确地评估药物暴露情况。特别是在C0/剂量比低的患者中，口服给药后他克莫司的峰值浓度可能会意外升高，导致毒性反应，并且（如已经显示的那样）导致长期移植物存活率低下。在另一个极端情况下，仅需要非常低剂量就能达到目标C0的患者可能峰值较低，AUC也较低，可能存在药物暴露不足的情况。本文将讨论C0的局限性，以及为实施更复杂的治疗药物监测提供证据所需的研究类型。本文重点关注成年肾移植受者的治疗。
