ArticleClinical pharmacokinetics2016
The Effect of Weight and CYP3A5 Genotype on the Population Pharmacokinetics of Tacrolimus in Stable Paediatric Renal Transplant Recipients.
Article in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- 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
- A Population Pharmacokinetic Model Does Not Predict the Optimal Starting Dose of Tacrolimus in Pediatric Renal Transplant Recipients in a Prospective Study: Lessons Learned and Model Improvement.Clinical pharmacokinetics · 2020Trial
- Population pharmacokinetics of tacrolimus in children with nephrotic syndrome.British journal of clinical pharmacology · 2018Trial
- A Review of Population Pharmacokinetic Models and Dosing Algorithms Assessing the Influence of CYP3A5 Genotype and Other Clinical Covariates on Tacrolimus Pharmacokinetics.Clinical pharmacokinetics · 2026Review
- A Novel Laboratory-Developed Test Using Multiplex qPCR to Further Personalize Tacrolimus Dosing.International journal of molecular sciences · 2026Article
- Population pharmacokinetics of tacrolimus and CYP3A5-driven variability: implications for model-informed dose individualization in pediatric renal transplant recipients.BMC pharmacology & toxicology · 2026Article
- Metabolic Acidosis Is Associated With an Accelerated Decline of Allograft Function in Pediatric Kidney Transplantation.Kidney international reports · 2024Article
- Pharmacogenetic Aspects of Drug Metabolizing Enzymes and Transporters in Pediatric Medicine: Study Progress, Clinical Practice and Future Perspectives.Paediatric drugs · 2023Review
- Immune cell function assays in the diagnosis of infection in pediatric liver transplantation: an open-labeled, two center prospective cohort study.Translational pediatrics · 2021Article
- Population pharmacokinetic analysis of tacrolimus in Chinese cardiac transplant recipients.European journal of hospital pharmacy : science and practice · 2020Article
- Off-label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics.British journal of clinical pharmacology · 2020Review
- Drug-metabolizing enzymes CYP3A as a link between tacrolimus and vitamin D in renal transplant recipients: is it relevant in clinical practice?Pediatric nephrology (Berlin, Germany) · 2019Review
- Population Pharmacokinetics of Tacrolimus in Transplant Recipients: What Did We Learn About Sources of Interindividual Variabilities?Journal of clinical pharmacology · 2019Review
- The potential impact of hematocrit correction on evaluation of tacrolimus target exposure in pediatric kidney transplant patients.Pediatric nephrology (Berlin, Germany) · 2019Article
- Clinical aspects of tacrolimus use in paediatric renal transplant recipients.Pediatric nephrology (Berlin, Germany) · 2019Review
- A Population Pharmacokinetic Model to Predict the Individual Starting Dose of Tacrolimus Following Pediatric Renal Transplantation.Clinical pharmacokinetics · 2018Article
- A new donors'Oncotarget · 2017Article
- Tacrolimus dose requirements in paediatric renal allograft recipients are characterized by a biphasic course determined by age and bone maturation.British journal of clinical pharmacology · 2017Article
- Economic Evaluation of Pharmacogenetic Tests in Patients Subjected to Renal Transplantation: A Review of Literature.Frontiers in public health · 2016Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aim of this study was to develop a population pharmacokinetic model of tacrolimus in paediatric patients at least 1 year after renal transplantation and simulate individualised dosage regimens. PATIENTS AND
methodsWe included 54 children with median age of 11.1 years (range 3.8-18.4 years) with 120 pharmacokinetic profiles performed over 2 to 4 h. The pharmacokinetic analysis was performed using the non-linear mixed-effects modelling software (NONMEM(®)). The impact of covariates including concomitant medications, age, the cytochrome P450 (CYP) CYP3A5*3 gene and the adenosine triphosphate binding cassette protein B1 (ABCB1) 3435 C→T gene polymorphism on tacrolimus pharmacokinetics was analysed. The final model was externally validated on an independent dataset and dosing regimens were simulated.
resultsA two-compartment model adequately described tacrolimus pharmacokinetics. Apparent oral clearance (CL/F) was associated with weight (allometric scaling) but not age. Children with lower weight and CYP3A5 expressers required higher weight-normalised tacrolimus doses. CL/F was inversely associated with haematocrit (P < 0.05) and γ-glutamyl transpeptidase (γGT) (P < 0.001) and was increased by 45 % in carriers of the CYP3A5*1 allele (P < 0.001). CL/F was not associated with concomitant medications. Dose simulations show that a daily tacrolimus dose of 0.2 mg/kg generates a pre-dose concentration (C 0) ranging from 5 to 10 µg/L depending on the weight and CYP3A5 polymorphism. The median area under the plasma concentration-time curve (AUC) corresponding with a tacrolimus C 0 of 4-8 µg/L was 97 h·µg/L (interquartile range 80-120).
conclusionsIn patients beyond the first year after transplantation, there is a cumulative effect of CYP3A5*1 polymorphism and weight on the tacrolimus C 0. Children with lower weight and carriers of the CYP3A5*1 allele have higher weight-normalised tacrolimus dose requirements.
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