ArticleTherapeutic drug monitoring2014
Effects of unbound mycophenolic acid on inosine monophosphate dehydrogenase inhibition in pediatric kidney transplant patients.
Article in Therapeutic drug monitoring, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Population pharmacokinetics of total and free mycophenolic acid in plasma in paediatric patients with nephrotic syndrome including salivary concentrations and the pharmacodynamics.Pharmacological reports : PR · 2026Article
- Clinical Model-Informed Precision Dosing Consult Service for Accelerating Personalized Medication in Pediatric Patients.Clinical pharmacology and therapeutics · 2026Review
- Pharmacokinetics of mycophenolic acid in plasma and peripheral blood mononuclear cells and its relationship with activity of inosine monophosphate dehydrogenase in Chinese adult kidney allograft recipients.Frontiers in pharmacology · 2025Article
- Efficacy and Safety of Pharmacokinetically-Driven Dosing of Mycophenolate Mofetil for the Treatment of Pediatric Proliferative Lupus Nephritis-A Double-Blind Placebo Controlled Clinical Trial (The Pediatric Lupus Nephritis Mycophenolate Mofetil Study).Journal of clinical trials · 2024Article
- Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies.Pharmaceutics · 2021Review
- Pharmacodynamic assessment of mycophenolic acid in resting and activated target cell population during the first year after renal transplantation.British journal of clinical pharmacology · 2020Article
- Mycophenolic Acid Derivatives with Immunosuppressive Activity from the Coral-Derived FungusMarine drugs · 2018Article
- Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure.Journal of clinical pharmacology · 2018Article
- Development of a Formula to Correct Particle-Enhanced Turbidimetric Inhibition Immunoassay Values so That it More Precisely Reflects High-Performance Liquid Chromatography Values for Mycophenolic Acid.Transplantation direct · 2018Article
- The pharmacokinetics and pharmacodynamics of mycophenolate mofetil in younger and elderly renal transplant recipients.British journal of clinical pharmacology · 2017Article
- The compelling case for therapeutic drug monitoring of mycophenolate mofetil therapy.Pediatric nephrology (Berlin, Germany) · 2017Review
- Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period.British journal of clinical pharmacology · 2014Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMycophenolic acid (MPA) is a key immunosuppressive drug that acts through inhibition of inosine monophosphate dehydrogenase (IMPDH). MPA is commonly measured, as part of therapeutic drug monitoring, as the total concentration in plasma. However, it has been postulated that the free (unbound) fraction of MPA (fMPA) is responsible for the immunosuppressive effects. In this study, a sensitive low volume high-performance liquid chromatography (HPLC) assay was developed to measure fMPA concentrations to explore the relationship between fMPA and IMPDH activity.
methodsTo obtain fMPA concentrations, plasma samples were filtrated using Centrifree ultrafiltration devices. The ultrafiltrate was analyzed by HPLC using a Kinetex C18 column (2.6 μm, 3.0 × 75 mm). fMPA concentrations were compared with the total MPA concentrations available in 28 pediatric kidney transplant patients at 3 consecutive occasions after transplantation. The relationship between fMPA and IMPDH activity was analyzed using an Emax model.
resultsThe HPLC assay, using 25 μL of the ultrafiltrates, was validated over a range from 2.5 to 1000 μL with good accuracy, precision, and reproducibility. Total and free MPA concentrations were well correlated (R = 0.85, P < 0.0001), although large intraindividual and interindividual variability in the bound MPA fractions was observed. The overall relationship between fMPA concentrations and IMPDH inhibition using the Emax model was comparable with that of total MPA, as previously reported. The model estimated EC50 value (164.5 μL) is in good agreement with reported in vitro EC50 values.
conclusionsThis study provides a simple HPLC method for the measurement of fMPA and a pharmacologically reasonable EC50 estimate. The good correlation between the total and free MPA concentrations suggests that routine measurement of fMPA to characterize mycophenolate pharmacokinetic and pharmacodynamic does not seem warranted, although the large variability in the bound fractions of MPA warrants further study.
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