Cyclosporine Lymphocyte Versus Whole Blood Pharmacokinetic Monitoring

Abstract

Cyclosporine (CyA) blood trough level (BTL), CyA dose pharmacokinetics, area under the curve (AUC), blood Cyclophylin (CyP) binding, and exposure index (EI) are often used as indicators of CyA efficacy and dose adjustment,1; 2 ; 3 despite conflicting results regarding their correlation with graft rejection and CyA nephrotoxicity.4; 5; 6; 7; 8; 9 ; 10 CyA immunosuppressive effect is initiated by its binding to its lymphocyte (Lc) receptor, the CyP.11 ; 12 It would be, therefore, more advantageous to monitor CyA pharmacokinetics at the site of action with the Lc by measuring intra-lymphocytic CyA trough level (LTL). Recent studies have shown a good correlation between CyA-CyP binding and its in vitro immunosuppressive activity. 13 ; 14 We hypothesized that drug-receptor interaction measurement might reflect more accurately the concentrations of biologically relevant compounds and hence may provide a better correlation with clinical events. The aim of our study was to compare CyA LTL to CyA BTL and dose in relation to 1) histological findings in renal transplant patients with graft dysfunction and 2) total lymphocyte count, a reflector of the state of immunosuppression.