ArticleBritish journal of clinical pharmacology2014
Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients.
Article in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Toward a robust tool for pharmacokinetic-based personalization of treatment with tacrolimus in solid organ transplantation: A model-based meta-analysis approach.British journal of clinical pharmacology · 2019Pooled it
- Efficacy and safety of tacrolimus in de novo pediatric transplant recipients randomized to receive immediate- or prolonged-release tacrolimus.Clinical transplantation · 2019Trial
- Population pharmacokinetics of tacrolimus in children with nephrotic syndrome.British journal of clinical pharmacology · 2018Trial
- Clinical Heterogeneity of Refractory Ascites After Pediatric Liver Transplantation Modulates Allograft Rejection Risk.MedComm · 2026Article
- Assessment of Telisotuzumab Vedotin Drug-Drug Interaction Potential Using Physiologically-Based Pharmacokinetic Modeling and Simulations.Journal of clinical pharmacology · 2025Article
- External assessment and refinement of a population pharmacokinetic model to guide tacrolimus dosing in pediatric heart transplant.Pharmacotherapy · 2023Article
- Evaluating risk factors for acute graft versus host disease in pediatric hematopoietic stem cell transplant patients receiving tacrolimus.Clinical and translational science · 2021Article
- Immune cell function assays in the diagnosis of infection in pediatric liver transplantation: an open-labeled, two center prospective cohort study.Translational pediatrics · 2021Article
- Early impact of donor CYP3A5 genotype and Graft-to-Recipient Weight Ratio on tacrolimus pharmacokinetics in pediatric liver transplant patients.Scientific reports · 2021Article
- Off-label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics.British journal of clinical pharmacology · 2020Review
- A Pediatric Covariate Function for CYP3A-Mediated Midazolam Clearance Can Scale Clearance of Selected CYP3A Substrates in Children.The AAPS journal · 2019Article
- Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models.Experimental and therapeutic medicine · 2019Article
- Population Pharmacokinetics of Tacrolimus in Transplant Recipients: What Did We Learn About Sources of Interindividual Variabilities?Journal of clinical pharmacology · 2019Review
- Predicting tacrolimus concentrations in children receiving a heart transplant using a population pharmacokinetic model.BMJ paediatrics open · 2017Article
- Population Pharmacokinetic Modelling and Bayesian Estimation of Tacrolimus Exposure: Is this Clinically Useful for Dosage Prediction Yet?Clinical pharmacokinetics · 2016Review
- Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in paediatric liver transplant recipients.British journal of clinical pharmacology · 2014Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation.
methodsThe present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates.
resultsThe final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: TVCL = 12.9 x (Weight/13.2)(0.75) x EXP(-0.00158 x TPT) x EXP(0.428 x CYP3A5) where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h(-1) kg(-1) (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%.
conclusionTacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance.
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