Cyclosporine absorption profiles in pediatric kidney and liver transplant patients

Abstract

Cyclosporine absorption profiling uses either the area under the concentration curve in the first 4 h post dose, AUC(0-4), or the concentration 2 h post dose (C2) to optimize immunosuppression in adult kidney and liver transplantation. We characterized C2 versus AUC(0-4) relationships over time after transplant and across transplant indications in 56 pediatric transplant patients. There were 36 kidney transplant patients aged 9.7+/-3.9 years. Nineteen of these patients were studied in the de novo period on day 7 post transplant and 17 in the maintenance phase more than 1 year post transplant. In addition, 20 liver transplant patients aged 8.9+/-4.2 years were studied in the maintenance phase. All patients had five blood samples collected over the 12-h dose interval that were analyzed by validated assay methods at a central laboratory. Pediatric C2 values were 1,463+/-658 ng/ml for de novo kidney, 954+/-322 ng/ml for maintenance kidney, and 619+/-339 ng/ml for maintenance liver transplant patients. C2 was a strong predictor of AUC(0-4) in all three pediatric groups, with coefficients of determination ( r(2)) ranging from 0.861 to 0.936. Although data were limited from the de novo period, the C2 versus AUC(0-4) regression was consistent over time after transplant and between transplant indications, with a regression slope of 2.50 in de novo kidney, 2.54 in maintenance kidney, and 2.76 in maintenance liver transplant recipients. These slopes were also comparable to that in adult maintenance kidney transplant patients (2.60). In conclusion, C2 versus AUC(0-4) relationships demonstrated consistency over time (de novo vs. maintenance phase), between transplant indications (kidney vs. liver), and across age groups (pediatric vs. adult patients). Average C2 values achieved with current pediatric cyclosporine dosing practices cluster around the target C2 ranges recommended for adults.