CHU Limoges, Department of Pharmacology and Toxicology, Limoges, France; INSERM, UMR 1248, Limoges, France; Univ Limoges, France.
CHU Limoges, Department of Pharmacology and Toxicology, Limoges, France; INSERM, UMR 1248, Limoges, France; Univ Limoges, France.
Pharmacol Res. 2018 Apr;130:316-321. doi: 10.1016/j.phrs.2018.02.016. Epub 2018 Feb 13.
Due to a high inter-individual variability in its pharmacokinetics, tacrolimus dose individualization is mandatory. Even though the expert opinion has defined the area under the curve (AUC) as the best marker to use when performing dose adjustment of tacrolimus, most centres only use trough levels. Multiple targets have been proposed for this parameter and physicians rely largely on their personal experience when making a decision about dose adjustment. Several population pharmacokinetics models (POPPK) allowing AUC determination have been developed, but only a few are actually used in routine practice for dose individualization. These POPPK models can also be used to perform Monte Carlo simulations that help to establish different dosing rules or to anticipate the pharmacokinetics of tacrolimus in particular populations, without conducting clinical trials. Various available applications of POPPK models to assist the prescriber in choosing the best tacrolimus dose are discussed in this paper as well as the difficulties in introducing them into routine therapeutic drug monitoring.
由于其药代动力学个体间差异很大，必须对他克莫司进行个体化剂量调整。尽管专家意见已将曲线下面积（AUC）定义为进行他克莫司剂量调整时使用的最佳标志物，但大多数中心仅使用谷浓度。针对该参数提出了多个目标，医生在决定调整剂量时主要依赖个人经验。已经开发出多个允许 AUC 确定的群体药代动力学模型（POPPK），但在常规实践中，只有少数用于个体化剂量。这些 POPPK 模型还可用于进行蒙特卡罗模拟，以帮助建立不同的给药规则或预测特定人群中他克莫司的药代动力学，而无需进行临床试验。本文讨论了 POPPK 模型在协助医生选择最佳他克莫司剂量方面的各种应用，以及在常规治疗药物监测中引入这些模型的困难。
