Evaluating tacrolimus pharmacokinetic models in adult renal transplant recipients with different CYP3A5 genotypes

European Journal of Clinical Pharmacology
Can HuXiao-cong Zuo

Abstract

Numerous studies have been conducted on the population pharmacokinetics of tacrolimus in adult renal transplant recipients. It has been reported that the cytochrome P450 (CYP) 3A5 genotype is an important cause of variability in tacrolimus pharmacokinetics. However, the predictive performance of population pharmacokinetic (PK) models of tacrolimus should be evaluated prior to their implementation in clinical practice. The aim of the study reported here was to test the predictive performance of these published PK models of tacrolimus. A literature search of the PubMed and Web of Science databases ultimately led to the inclusion of eight one-compartment models in our analysis. We collected a total of 1715 trough concentrations from 174 patients. Predictive performance was assessed based on visual and numerical comparison bias and imprecision and by the use of simulation-based diagnostics and Bayesian forecasting. Of the eight one-compartment models assessed, seven showed better predictive performance in CYP3A5 extensive metabolizers in terms of bias and imprecision. Results of the simulation-based diagnostics also supported the findings. The model based on a Chinese population in 2013 (model 3) showed the best and most stable pre...Continue Reading

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Citations

Apr 7, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Moataz E MohamedUNKNOWN DeKAF Genomics and GEN03 Investigators
Aug 13, 2020·Clinical Pharmacokinetics·Ranita KirubakaranJane E Carland
Jan 14, 2021·Transplantation Direct·Ehsan NobakhtSherry Dadgar
Jun 14, 2021·Drug Discovery Today·Tom C ZwartDirk Jan A R Moes
Aug 29, 2019·ACS Omega·Marwan Abdelmahmoud Abdelkarim MakiAbu Bakar Bin Abdul Majeed
Sep 25, 2021·British Journal of Clinical Pharmacology·Ranita KirubakaranSophie L Stocker
Nov 25, 2021·European Journal of Drug Metabolism and Pharmacokinetics·Janthima MethaneethornNattawut Leelakanok

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Methods Mentioned

BETA
Assay

Software Mentioned

R
R Foundation for Statistical
ICON
R package ( NPDE
NONMEM

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