ArticleEuropean journal of drug metabolism and pharmacokinetics2019
Population Pharmacokinetic Analysis of Immediate-Release Oral Tacrolimus Co-administered with Mycophenolate Mofetil in Corticosteroid-Free Adult Kidney Transplant Recipients.
Article in European journal of drug metabolism and pharmacokinetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 5 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 5 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- 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
- A Systematic Review of Multiple Linear Regression-Based Limited Sampling Strategies for Mycophenolic Acid Area Under the Concentration-Time Curve Estimation.European journal of drug metabolism and pharmacokinetics · 2021Pooled it
- Population Pharmacokinetic Models of Tacrolimus in Adult Transplant Recipients: A Systematic Review.Clinical pharmacokinetics · 2020Pooled it
- Predictability of Capillary Blood Spot Toward Venous Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus in Solid Organ Transplant Recipients.European journal of drug metabolism and pharmacokinetics · 2019Pooled it
- Impacts of Uremic Toxins on the Population Pharmacokinetics of Total Mycophenolic Acid and its Glucuronide Metabolite in Adult Kidney Transplant Recipients.Clinical pharmacokinetics · 2026Observational
- Population Pharmacokinetic Modelling of Unbound Mycophenolic Acid and its Glucuronide in Adult Kidney Transplant Recipients in Early Post-Transplant.Clinical pharmacokinetics · 2026Observational
- Analytical Models to Optimize Tacrolimus Dosing in Solid Organ Transplantation: A Systematic Review.Pharmaceutics · 2026Review
- Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.Clinical pharmacokinetics · 2023Article
- Predictive Performance of Published Tacrolimus Population Pharmacokinetic Models in Thai Kidney Transplant Patients.European journal of drug metabolism and pharmacokinetics · 2022Article
- CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients.Frontiers in pharmacology · 2021Article
- Comparisons of Four Protein-Binding Models Characterizing the Pharmacokinetics of Unbound Phenytoin in Adult Patients Using Non-Linear Mixed-Effects Modeling.Drugs in R&D · 2020Article
- Population Pharmacokinetics of Mycophenolic Acid Co-Administered with Tacrolimus in Corticosteroid-Free Adult Kidney Transplant Patients.Clinical pharmacokinetics · 2019Observational
- Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveTacrolimus is the mainstay calcineurin inhibitor frequently administered with mycophenolic acid with or without corticosteroids to prevent graft rejection in adult kidney transplant recipients. The primary objective of this study was to develop and evaluate a population pharmacokinetic model characterizing immediate-release oral tacrolimus co-administered with mycophenolate mofetil (a pro-drug of mycophenolic acid) in adult kidney transplant recipients on corticosteroid-free regimens. The secondary objective was to investigate the effects of clinical covariates on the pharmacokinetics of tacrolimus, emphasizing the interacting effects of mycophenolic acid.
methodsPopulation modeling and evaluation were conducted with Monolix (Suite-2018R1) using the stochastic approximation expectation-maximization algorithm in 49 adult subjects (a total of 320 tacrolimus whole-blood concentrations). Effects of clinical variables on tacrolimus pharmacokinetics were determined by population covariate modeling, regression modeling, and categorical analyses.
resultsA two-compartment, first-order absorption with a lag-time, linear elimination, and constant error model best represented the population pharmacokinetics of tacrolimus. The apparent clearance value for tacrolimus was 17.9 l/h (6.95% relative standard error) in our model, which is lower compared with similar subjects on corticosteroid-based therapy. The glomerular filtration rate had significant effects on the apparent clearance and central compartment volume of distribution. Conversely, mycophenolic acid did not affect the apparent clearance of tacrolimus.
conclusionWe have developed and internally evaluated a novel population pharmacokinetic model for tacrolimus co-administered with mycophenolate mofetil in corticosteroid-free adult kidney transplant patients. These findings are clinically important and provide further reasons for conducting therapeutic drug monitoring in this specific population.
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