Aim: Cyclosporine A (CsA) is highly variable pharmacokinetically and has a narrow therapeutic window; the serum level of patients treated with CsA must be monitored carefully. We investigated the trough and second-hour serum levels of CsA, the calculated area under the curve (AUC), and their association of those factors with chronic allograft dysfunction in pediatric patients.Methods: Fifteen renal allograft recipients (8 boys and 7 girls; mean age, 15.2 ± 3.5 years) who were undergoing treatment with cyclosporine were included in the study. The patients were divided into 2 groups according to the serum creatinine level and the presence of proteinuria: The "stable" group (n = 10, serum creatinine level < 1. 5 mg/dL, no proteinuria) and the "chronic allograft dysfunction (CAD)" group (n = 5, serum creatinine level > 1.5, and/or daily protein excretion > 4 mg/m 2 /h). Trough (C 0 ) and second-hour (C 2 ) cyclosporine serum levels were measured, and AUC values was calculated according to the formula (AUC = 990 + 10.74 × C 0 + 2.28 × C 2 ).
Results:The mean duration of post transplant follow-up was 25 ± 23 months (range, 8-72 months). The mean cyclosporine dose was 4.8 ± 1.4 mg/kg/d. The mean C 0, C 2, and calculated AUC values were 91.5 ± 62.1 ng/mL, 561.2 ± 241.5 ng/mL, and 3380 ± 996 ng.h/mL, respectively. Patients in the stable group had a history of fewer acute rejection episodes than did patients with CAD (P < 0.05). Calculated AUC values in the patients with CAD were significantly higher than in the stable patients. C 0 and C 2 levels did not correlate with CAD.
Conclusion:In the monitoring of cyclosporine dosing for the follow-up of CAD, calculated AUC values may be a better parameter than levels of C 0 or C 2 alone.