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Pediatric Nephrology
Published in: Pediatric Nephrology 6/2014

Open Access 01-06-2014 | Original Article

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

Authors: Anne-Laure Lapeyraque, Nastya Kassir, Yves Théorêt, Maja Krajinovic, Marie-José Clermont, Catherine Litalien, Véronique Phan

Published in: Pediatric Nephrology | Issue 6/2014

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Abstract

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 (AUC0–24), minimum whole-blood concentration (Cmin), maximum whole-blood concentration (Cmax), and time to achieve maximum whole-blood concentration (tmax)] were compared between Tac formulations and between CYP3A5 and MDR1 genotypes after dose normalization.

Results

Both AUC0–24 and Cmin 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 AUC0–24 was 90.8 %, with 90 % CI limits of 85.3 to 96.7 %, falling within bioequivalence limits. The CYP3A5 genotype influences the dose-normalized Cmin with the twice-daily formulation only.

Conclusions

Both tacrolimus formulations are bioequivalent in pediatric renal recipients. However, we observed a decrease in AUC0–24 and Cmin after the conversion, requiring close pharmacokinetic monitoring during the conversion period.
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Metadata
Title
Conversion from twice- to once-daily tacrolimus in pediatric kidney recipients: a pharmacokinetic and bioequivalence study
Authors
Anne-Laure Lapeyraque
Nastya Kassir
Yves Théorêt
Maja Krajinovic
Marie-José Clermont
Catherine Litalien
Véronique Phan
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-013-2724-0

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