ArticleClinical journal of the American Society of Nephrology : CJASN2011
Nonlinear relationship between mycophenolate mofetil dose and mycophenolic acid exposure: implications for therapeutic drug monitoring.
Article in Clinical journal of the American Society of Nephrology : CJASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 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
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Clinical Significance of Therapeutic Drug Level Monitoring for Mycophenolate in Patients With Extrarenal Systemic Lupus Erythematosus-A Systematic Review and Meta-Analysis.Arthritis care & research · 2026Pooled it
- A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.Journal of Zhejiang University. Science. B · 2025Guideline
- Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co-administered with tacrolimus.British journal of clinical pharmacology · 2019Pooled it
- A Mycophenolate Pharmacokinetic Study with New Insights into Enterohepatic Recirculation in Kidney Transplant Recipients.Clinical pharmacokinetics · 2026Trial
- Bayesian estimation of mycophenolate mofetil in lung transplantation, using a population pharmacokinetic model developed in kidney and lung transplant recipients.Clinical pharmacokinetics · 2012Trial
- Pharmacokinetic Covariates Influencing Mycophenolate Area Under the Curve in a Danish Renal Transplant Population.Pharmaceutics · 2026Article
- Simultaneous Prediction of Area Under the Curves of Mycophenolic Acid and Its Metabolites and Enterohepatic Recirculation in Kidney Transplant Recipients.Therapeutic drug monitoring · 2025Observational
- Limited Sampling Strategies Fail to Accurately Predict Mycophenolic Acid Area Under the Curve in Kidney Transplant Recipients and the Impact of Enterohepatic Recirculation.Therapeutic drug monitoring · 2025Article
- Significant Effects of Renal Function on Mycophenolic Acid Total Clearance in Pediatric Kidney Transplant Recipients with Population Pharmacokinetic Modeling.Clinical pharmacokinetics · 2023Article
- Population Pharmacokinetics of Mycophenolic Acid in Renal Transplant Patients: A Comparison of the Early and Stable Posttransplant Stages.Frontiers in pharmacology · 2022Article
- Population pharmacokinetics of mycophenolate mofetil in pediatric patients early after liver transplantation.Frontiers in pharmacology · 2022Article
- Population Pharmacokinetics of Enteric-Coated Mycophenolate Sodium in Children after Renal Transplantation and Initial Dosage Recommendation Based on Body Surface Area.Computational and mathematical methods in medicine · 2022Article
- Association of ABCC2 Haplotypes to Mycophenolic Acid Pharmacokinetics in Stable Kidney Transplant Recipients.Journal of clinical pharmacology · 2021Article
- Improvements in the Oral Absorption and Anticancer Efficacy of an Oxaliplatin-Loaded Solid Formulation: Pharmacokinetic Properties in Rats and Nonhuman Primates and the Effects of Oral Metronomic Dosing on Colorectal Cancer.International journal of nanomedicine · 2020Article
- Effect of Protein Binding on Exposure of Unbound and Total Mycophenolic Acid: A Population Pharmacokinetic Analysis in Chinese Adult Kidney Transplant Recipients.Frontiers in pharmacology · 2020Article
- Pharmacokinetics and Pharmacodynamics of Immediate- and Modified-Release Mycophenolic Acid Preparations in Healthy Beagle Dogs.Frontiers in veterinary science · 2020Article
- Population Pharmacokinetics of Mycophenolic Acid Co-Administered with Tacrolimus in Corticosteroid-Free Adult Kidney Transplant Patients.Clinical pharmacokinetics · 2019Observational
- Influence of Calcineurin Inhibitor and Sex on Mycophenolic Acid Pharmacokinetics and Adverse Effects Post-Renal Transplant.Journal of clinical pharmacology · 2019Article
- Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention.Transplantation · 2019Review
- 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
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesMycophenolate mofetil (MMF) is an immunosuppressive drug used in renal transplant patients. Upon oral administration it is hydrolyzed to the active agent mycophenolic acid (MPA). In renal transplant recipients, MMF therapy is optimal when the area under the curve of MPA is 30 to 60 mg·h/L. When MMF doses are adjusted, a linear relationship between dose and MPA exposure is assumed. In this study, the linearity of MMF pharmacokinetics was investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: MPA concentration-time profiles from renal transplant recipients cotreated with cyclosporine (n = 140) or tacrolimus (n = 101) were analyzed retrospectively using nonlinear mixed-effects modeling. The correlation between the MMF dose and the pharmacokinetics parameters was evaluated.
resultsIn the developed population pharmacokinetics model MPA clearance and the central volume of distribution were correlated with cyclosporine coadministration and time posttransplantation. The pharmacokinetics of MPA were not linear. Bioavailability decreased with increasing MMF doses. Compared with an MMF dose of 1000 mg (=100%), relative bioavailability was 123%, 111%, 94%, and 90% in patients receiving MMF doses of 250, 500, 1500, and 2000 mg in combination with cyclosporine (P < 0.001); respective values in tacrolimus-cotreated patients were 176%, 133%, 85%, and 76% (P < 0.001). Because of the decreasing relative bioavailability, MPA exposure will increase less than proportionally with increasing MMF doses.
conclusionsMMF exhibits nonlinear pharmacokinetics. This should be taken into account when performing therapeutic drug monitoring.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.