[Therapeutic monitoring of immunosuppressive drugs: interest of calcineurin activity assessment in liver transplantation].
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.
Laboratoire de pharmacologie et toxicologie, CHU Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94000 Créteil, France. benoit.blanchet@hmn.aphp.fr
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D019703:Calcineurin / Q000097:blood*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology; D016903:Drug Monitoring; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D016031:Liver Transplantation / Q000502:physiology*; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus