Circadian variations in cyclosporine C2 concentrations during the first 2 weeks after liver transplantation

The strategies currently used to monitor concentrations of cyclosporine (CsA) in transplanted patients include whole blood trough (CO), total or abbreviated area under the curve (AUC) concentration and population pharmacokinetic approaches. Recently, a single blood concentration measurement at 2 hours (C2) after CsA administration has been shown to be helpful to predict clinical effects during the first weeks after transplantation of liver and kidney grafts. However, this approach has raised multiple questions about pharmacokinetic variability, analytical methods, and organizational requirements. From a pharmacokinetic point of view, the variability of CsA blood concentrations may relate to circadian variations. The present study sought to characterize the circadian variation in C0 and C2 CsA levels among 20 liver transplant recipients during the first 2 weeks posttransplant. All patients received two equal oral doses of CsA microemulsion formulation every 12 hours. Blood samples were collected before and 2 hours after CsA administration in the morning (Am) and in the evening (pm). Whole blood concentrations of CsA were assayed using the monoclonal fluorescence polarization immunoassay system. During the first 2 weeks posttransplant, C2 AM mean levels were significantly higher than C2 Pm levels (542 +/- 241 vs 383 +/- 182 ng/mL, P = .005), while the C0 AM mean level was not statistically different from the C0 Pm (285 +/- 174 vs 223 +/- 124 ng/mL, P = .367). Our results suggest that morning CsA blood samples may afford a better approach to optimize the CsA dosage, especially based on C2 values.