Improved pharmacokinetic monitoring of tacrolimus exposure after pediatric renal transplantation

Abstract

Because of its narrow therapeutic index, monitoring of drug exposure is recommended for tacrolimus (T). Limited data are available on kinetics of T in children after transplantation. Our study investigated the correlation between T trough and the area under the time-concentration curve (AUC) in pediatric renal transplant recipients and investigated the effect of steroids. Data on T troughs and two h and four h post-dose concentrations over the first post-transplant year in 20 transplant recipients from August 2001 to June 2005 were analyzed. Patients were analyzed in two groups based on their use of steroids. Although the overall correlation between the troughs and AUC was good (r = 0.85, Pearson test), during the first month the correlation was poor in the cohort receiving steroids (r = 0.5) compared with those on a steroid minimization regimen (r = 0.9). In 85% of patients there was a discrepancy between the trough and AUC leading to errors in dose adjustment. In conclusion, although the overall correlation between T trough and AUC is good, it is suboptimal in the first post-transplant month in children receiving steroids. Because of large variation in exposure, we recommend AUC monitoring for T. Prospective studies are needed to determine the impact of more accurate monitoring of T exposure on outcomes.