PHARMACOKINETIC PROFILE OF ASIAN PEDIATRIC RENAL TRANSPLANT RECIPIENTS BY SPARSE SAMPLING AUC

Abstract

P694 Aims: Evaluate pharmacokinetics of micro emulsion cyclosporine in Asian pediatric live related renal transplant recipients. Methods: Seventy eight children received live related renal transplants. Sparse sampling area under the curve (AUC) was undertaken in all on 5th day of transplant. AUC was done by estimating C0, C2 and C6 levels and substituting C0 for C12 and AUC determined by a computer programme. The dose of CyA was 10mg/kg/day in two divided doses (BD) or in three doses (TDS). An AUC of 6000 – 8000 ng/ml/hr was taken as adequate for BD and 4000 – 5000 for a TDS dose. Results: The mean AUC was 7400 ± 1659 and the mean C0 was 312 ± 116 and C2 1296 ± 354. Of the 78, 41 (52%) had adequate AUC. Twenty four (31%) were rapid metabolizers (AUC < 6000) and 17% were slow metabolizers (AUC > 8000) and required dose reduction. Of the 24 with low AUC, 20 did not respond to dose increments and were placed on TDS dose at 10mg/kg/day. The mean AUC was 4814 ± 1132 in TDS dose. Rejection episodes were 42% in BD dose and 38% in TDS dose (p=0.1). One year graft survival was 90% in both groups. The correlation of C0 vs AUC was 0.54 (p=0.005) and C2 vs AUC was 0.45 (p=0.02). All 78 recipients required dose readjustments within the first three months. In all 40 (51%) required repeated AUC’s for dose monitoring. Conclusions: The metabolism of CyA is unpredictable in our children and no monitoring parameter C0 or C2 is a safe option in the early transplant period. A 3 point AUC provided the best guide to overall exposure. Changes from BD to TDS doses were more important in the early transplant period to maintain adequate levels.