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Title: In Vivo CYP3A4 Activity, CYP3A5 Genotype, and Hematocrit Predict Tacrolimus Dose Requirements and Clearance in Renal Transplant Patients
Authors: de Jonge, H ×
de Loor, H
Verbeke, Kristin
Vanrenterghem, Yves
Kuypers, Dirk #
Issue Date: Sep-2012
Publisher: Mosby
Series Title: Clinical Pharmacology and Therapeutics vol:92 issue:3 pages:366-375
Article number: 10.1038/clpt.2012.109
Abstract: Tacrolimus is metabolized by CYP3A4 and CYP3A5 and is characterized by a narrow therapeutic index and highly variable pharmacokinetics. This cross-sectional study in 59 renal transplant patients investigated the relationship among in vivo CYP3A4 activity (assessed using midazolam as a drug probe), CYP3A5 genotype on the one hand, and tacrolimus pharmacokinetics on the other hand, taking into account other potential determinants of tacrolimus disposition. In vivo CYP3A4 activity and CYP3A5 genotype explain 56-59% of variability in tacrolimus dose requirements and clearance, contributing ~25 and 30%, respectively. Hematocrit explains an additional 4-14%. These data indicate that CYP3A4- and CYP3A5-mediated tacrolimus metabolisms are major determinants of tacrolimus disposition in vivo and explain a substantial part of the clinically observed high interindividual variability in tacrolimus pharmacokinetics. Furthermore, these data provide a potential basis for a comprehensive approach to predicting tacrolimus dose requirement in individual patients and hence provide a strategy to tailor immunosuppressive therapy in transplant recipients.
URI: 
ISSN: 0009-9236
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Research in GastroIntestinal Disorders
Laboratory of Nephrology
× corresponding author
# (joint) last author

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