Blanchet B
Laboratoire de pharmacologie et toxicologie, CHU Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France.
Ann Pharm Fr. 2008 Mar;66(2):96-101. doi: 10.1016/j.pharma.2008.03.003. Epub 2008 May 27.
Therapeutic monitoring of calcineurin inhibitors (ciclosporin and tacrolimus) consists in pharmacokinetic monitoring. Pharmacodynamics based on calcineurin activity may be particularly interesting in liver transplantation due to the large intra- and interindividual variability of pharmacokinetics of ciclosporin and tacrolimus. A recent investigation on the pharmacokinetic-pharmacodynamic relationship of tacrolimus showed that monitoring of calcineurin activity in PBMC may be particularly relevant within the first three post-transplantation months. Thereafter, the monitoring of trough blood concentrations of tacrolimus remains adequate. Moreover, two clinical investigations carried out within the early and late post-transplantation periods reported a promising result which is a positive correlation between calcineurin activity and incidence of graft rejection, whatever graft type and calcineurin inhibitors. In each study, transplanted recipients with a graft rejection exhibited a greater trough calcineurin activity compared to patients without graft rejection. However, prospective investigations are required because of the small cohorts of patients enrolled in both studies. The aim of these investigations will be to confirm the interest of calcineurin activity monitoring as a marker of cellular immunity and its positive link with pharmacokinetic monitoring.
钙调神经磷酸酶抑制剂（环孢素和他克莫司）的治疗监测包括药代动力学监测。由于环孢素和他克莫司药代动力学在个体内和个体间存在较大差异，基于钙调神经磷酸酶活性的药效学在肝移植中可能特别有意义。最近一项关于他克莫司药代动力学 - 药效学关系的研究表明，在移植后的前三个月内监测外周血单个核细胞中的钙调神经磷酸酶活性可能尤为重要。此后，监测他克莫司的血药谷浓度就足够了。此外，在移植后早期和晚期进行的两项临床研究报告了一个有前景的结果，即无论移植器官类型和钙调神经磷酸酶抑制剂如何，钙调神经磷酸酶活性与移植排斥发生率之间呈正相关。在每项研究中，发生移植排斥的受者相比未发生移植排斥的患者，其钙调神经磷酸酶血药谷活性更高。然而，由于这两项研究纳入的患者队列较小，需要进行前瞻性研究。这些研究的目的将是证实监测钙调神经磷酸酶活性作为细胞免疫标志物的意义及其与药代动力学监测的正向联系。
