Cyclosporine monitoring in peripheral blood mononuclear cells: feasibility and interest. A prospective study on 20 renal transplant recipients.
Cyclosporine (CsA) has potent immunosuppressive properties, reflecting its ability to block the transcription of cytokine genes (mainly interleukin 2) in CD4+ T lymphocytes, markedly improving transplantation outcomes in the past 20 years. CsA pharmacokinetic variability and renal toxicity require whole blood (WB) monitoring by 4-hour area under the drug concentration curves (AUC0-4) or 2-hour postdose concentration (C2) monitoring. Nevertheless, graft rejection can occur despite target blood levels, suggesting that WB monitoring does not guarantee optimal immunosuppression. For a decade, pharmacologists and clinicians have worked to optimize CsA doses; some authors, inspired by its mechanism of action, have proposed therapeutic drug monitoring using peripheral blood mononuclear cells (PBMC; lymphocytes and monocytes). The aim of this study was to assess the feasibility and interest of CsA monitoring in PBMC ([CsA]PBMC). We also measured in vitro distribution of CsA in CD4+ and CD4- subsets.
Lepage
J M
JM
Service de Pharmacologie, Centre Hospitalier Régional et Universitaire, Caen, France.
Lelong-Boulouard
V
V
Lecouf
A
A
Debruyne
D
D
Hurault de Ligny
B
B
Coquerel
A
A
D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000097:blood* / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011446:Prospective Studies
D016572:Cyclosporine