Monitoring of tacrolimus concentrations in peripheral blood mononuclear cells: application to cardiac transplant recipients

International audience; OBJECTIVES: Despite the intensive therapeutic drug monitoring of tacrolimus (TAC) using trough whole blood concentrations, graft rejections occur in transplant recipient patients. Thus, other ways to monitor closely immunosuppressive treatments are necessary. A promising way of monitoring TAC treatments could be the measure of its concentrations inside of the lymphocyte cell. Whereas the pharmacokinetics of TAC in peripheral blood mononuclear cells (PBMCs) was evaluated in renal and liver transplant recipients, data regarding PBMC concentrations of TAC in cardiac transplant recipients are lacking. This study aimed, in cardiac transplant recipients: to validate a method for determination of TAC in PBMC, to investigate PBMC trough concentrations of TAC, and to evaluate their relationship with trough whole blood concentrations. DESIGN AND METHOD: We developed and validated a High-performance-liquid-chromatography tandem mass-spectrometry method of TAC quantitation in PBMC. The method was then evaluated by determining TAC concentrations in PBMC of 24 cardiac transplant recipients. RESULTS: Twenty-four patients were prospectively included in the study. Tacrolimus PBMC concentrations displayed a large inter-individual pharmacokinetic variability (CV=71.4%) in the cohort. A lack of correlation between TAC whole blood trough concentrations and TAC trough concentrations in PBMCs was found (r=0.259; p=0.183). CONCLUSION: Further studies should be implemented to evaluate the correlation between TAC concentrations in PBMC and clinical outcomes in cardiac transplant recipients to allow concluding whether monitoring TAC concentrations in PBMC is a good tool to prevent graft rejection in cardiac recipients.