ArticleClinical pharmacokinetics2017
A New CYP3A5*3 and CYP3A4*22 Cluster Influencing Tacrolimus Target Concentrations: A Population Approach.
Article in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 4 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Accelerating tacrolimus model-informed precision dosing in kidney transplant recipients: Model evaluation and refinement strategies.British journal of clinical pharmacology · 2026Pooled it
- Model-Informed Precision Dosing of Tacrolimus: A Systematic Review of Population Pharmacokinetic Models and a Benchmark Study of Software Tools.Clinical pharmacokinetics · 2024Pooled it
- Population Pharmacokinetic Models of Tacrolimus in Adult Transplant Recipients: A Systematic Review.Clinical pharmacokinetics · 2020Pooled 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
- Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus inTransplant international : official journal of the European Society for Organ Transplantation · 2022Trial
- 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
- 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
- Analytical Models to Optimize Tacrolimus Dosing in Solid Organ Transplantation: A Systematic Review.Pharmaceutics · 2026Review
- Effect of CYP3A4 Methylation on Tacrolimus Pharmacokinetics.Therapeutic drug monitoring · 2025Article
- Optimizing Dose Conversion from IR-Tac to LCP-Tac Formulations in Renal Transplant Recipients: A Population Pharmacokinetic Modeling Study.Pharmaceutics · 2025Article
- A Population Pharmacokinetic Model and Dosing Algorithm to Guide the Tacrolimus Starting and Follow-Up Dose in Living and Deceased Donor Kidney Transplant Recipients.Clinical pharmacokinetics · 2025Article
- Analysis of Tacrolimus Clearance in Patients with Kidney Transplants from Romania.Biomedicines · 2025Article
- Trends in Precision Medicine and Pharmacogenetics as an Adjuvant in Establishing a Correct Immunosuppressive Therapy for Kidney Transplant: An Up-to-Date Historical Overview.International journal of molecular sciences · 2025Review
- State of Art of Dose Individualization to Support tacrolimus drug monitoring: What's Next?Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients.Diagnostics (Basel, Switzerland) · 2024Article
- The effect of genetic variants in the transcription factor TSPYL family on the CYP3A4 mediated cyclosporine metabolism in kidney transplant patients.Clinical and translational science · 2024Article
- The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events.The pharmacogenomics journal · 2024Article
- Guiding the starting dose of the once-daily formulation of tacrolimus in "Frontiers in pharmacology · 2024Article
- Article
- Pharmacogenetics of Drug Metabolism: The Role of Gene Polymorphism in the Regulation of Doxorubicin Safety and Efficacy.Cancers · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSingle nucleotide polymorphisms (SNPs) in the CYP3A5 and CYP3A4 genes have been reported to be an important cause of variability in the pharmacokinetics of tacrolimus in renal transplant patients. The aim of this study was to merge all of the new genetic information available with tacrolimus pharmacokinetics to generate a more robust population model with data from renal transplant recipients.
methodsTacrolimus exposure data from 304 renal transplant recipients were collected throughout the first year after transplantation and were simultaneously analyzed with a population pharmacokinetic approach using NONMEM
resultsThe tacrolimus whole-blood concentration versus time data were best described by a two-open-compartment model with inter-occasion variability assigned to plasma clearance. The following factors led to the final model, which significantly decreased the minimum objective function value (p < 0.001): a new genotype cluster variable combining the CYP3A5*3 and CYP3A4*22 SNPs defined as extensive, intermediate, and poor metabolizers; the standardization of tacrolimus whole blood concentrations to a hematocrit value of 45%; and age included as patients <63 years versus patients ≥63 years. External validation confirmed the prediction ability of the model with median bias and precision values of 1.17 ng/mL (95% confidence interval [CI] -3.68 to 4.50) and 1.64 ng/mL (95% CI 0.11-5.50), respectively. Simulations showed that, for a given age and hematocrit at the same fixed dose, extensive metabolizers required the highest doses followed by intermediate metabolizers and then poor metabolizers.
conclusionsTacrolimus disposition in renal transplant recipients was described using a new population pharmacokinetic model that included the CYP3A5*3 and CYP3A4*22 genotype, age, and hematocrit.
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