Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study

BACKGROUND: The objectives of this study were to investigate pharmacokinetic and pharmacogenetic parameters during the conversion on a 1:1 (mg:mg) basis from a twice-daily (Prograf) to once-daily (Advagraf) tacrolimus formulation in pediatric kidney transplant recipients. METHODS: Twenty-four-hour pharmacokinetic profiles were analyzed before and after conversion in 19 stable renal transplant recipients (age 7–19 years). Tacrolimus pharmacokinetic parameters [area under the concentration-time curve (AUC(0–24)), minimum whole-blood concentration (C(min)), maximum whole-blood concentration (C(max)), and time to achieve maximum whole-blood concentration (t(max))] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization. RESULTS: Both AUC(0–24) and C(min) decreased after conversion (223.3 to 197.5 ng.h/ml and 6.5 to 5.6 ng/ml; p = 0.03 and 0.01, respectively). However, the ratio of the least square means (LSM) for AUC(0–24) was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized C(min) with the twice-daily formulation only. CONCLUSIONS: Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC(0–24) and C(min) after the conversion, requiring close pharmacokinetic monitoring during the conversion period.