Pharmacokinetics of tacrolimus in stable paediatric renal transplant recipients.
Because tacrolimus (Tac) has a narrow therapeutic index and highly inter- and intra-individual variable pharmacokinetic (PK) characteristics, monitoring of drug exposure is recommended, but limited data are available on the kinetics of Tac in paediatric renal transplant recipients, especially of limited sampling strategies. To investigate the correlation between Tac trough level (TL) and the 0-12 h area under the curve (AUC), and the value of abbreviated AUC monitoring, we evaluated 12 h PK profiles in 27 children at least 1 year after transplantation. There was a significant discrepancy between Tac TLs and 0-12 h AUC (r = 0.60). Every time point, different from C(0), gave a better prediction for the drug exposure, with C(4) and C(6) as best predictors (r = 0.93 and r = 0.92, respectively). The 0-12 h AUC was estimated with great precision by the use of a two- or three-point sampling strategy, and the latter is more time-point independent. In paediatric renal transplant recipients on Tac maintenance therapy, whose condition is stable, Tac TL is not a reliable tool for the estimation of drug exposure. Abbreviated monitoring, especially at three points in time, give reliable predictions of the complete 0-12 h AUC. We suggest a 0-12 h AUC of around 150 ng x h/ml for stable paediatric renal transplant recipients 1 year after transplantation and around 100 ng x h/ml in the following years. Target AUC values should be further established for paediatric transplant recipients according to the time after transplantation.
Claeys
Tania
T
Department of Paediatric Medicine, University Hospital Leuven, Herestraat 49, Louvain, 3000 Vlaams-Brabant, Belgium. Tania.Claeys@uz.kuleuven.ac.be
Van Dyck
Maria
M
Van Damme-Lombaerts
Rita
R
D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007223:Infant; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D016559:Tacrolimus / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D016559:Tacrolimus