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Updated: Feb 8, 2026
Robot-Assisted Kidney Transplantation
Published on: July 19, 2021
A Mycophenolate Pharmacokinetic Study with New Insights into Enterohepatic Recirculation in Kidney Transplant
Moataz E Mohamed1, Abdelrahman Saqr1, Guillaume Onyeaghala2
1Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 7-151 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN, 55455, USA.
Background:
Mycophenolic acid (MPA) has complex pharmacokinetics in part due to enterohepatic recirculation (EHR). A deeper understanding of MPA pharmacokinetics and specifically how EHR and patterns of EHR affect exposure will improve immunosuppression outcomes. This study provides a contemporary and comprehensive assessment of MPA and metabolites in the blood and urine with a focus on EHR characteristics.
Methods:
Kidney transplant recipients (n = 84) receiving mycophenolate mofetil (MMF) and tacrolimus underwent an intensive MPA pharmacokinetic assessment. Pharmacokinetics of MPA and its metabolites, EHR%, and number of secondary peaks were determined. The associations between EHR, the number of secondary peaks, and achievement of MPA therapeutic range were studied. MMF dose proportionality with MPA exposure was evaluated.
Results:
MPA exhibited high pharmacokinetic variability, with 5.5-fold differences in AUC0-12, 18.4-fold differences in trough concentrations, and a 3.4-fold difference in EHR%. Median MPA EHR% was 40.5%. There were no significant associations between EHR% and MPA AUC0-12 or trough. MPA AUC0-12 and trough were significantly associated with the number of MPA secondary peaks (0, 1, or ≥ 2 peaks). Participants without secondary peaks showed the highest percentage of subtherapeutic MPA AUC0-12 and troughs, while participants with ≥ 2 peaks were more likely to be supratherapeutic.
Conclusions:
There was no association between the EHR% and MPA AUC0-12 or trough. We identified three distinct patterns of MPA secondary peaks (0, 1, or ≥ 2 peaks), which were significantly associated with MPA AUC0-12 and trough. Studies to evaluate the relationship of MPA EHR measures and clinical outcomes are needed.
Trial Registry:
Clinical Trial Notation: clinicaltrials.gov, NCT04953715.
Insights
Enterohepatic recirculation (EHR) patterns, not the percentage, significantly impact mycophenolic acid (MPA) levels in kidney transplant patients. Understanding secondary peaks is crucial for optimizing immunosuppression with mycophenolate mofetil (MMF).
Area of Science:
- Pharmacology
- Transplant Medicine
- Clinical Chemistry
Background:
- Mycophenolic acid (MPA) pharmacokinetics are complex, influenced by enterohepatic recirculation (EHR).
- Optimizing immunosuppression requires a deeper understanding of MPA exposure and EHR patterns.
- This study comprehensively assesses MPA and its metabolites, focusing on EHR characteristics.
Purpose of the Study:
- To comprehensively assess MPA and metabolite pharmacokinetics in kidney transplant recipients.
- To investigate the impact of enterohepatic recirculation (EHR) and its patterns on MPA exposure.
- To determine the association between EHR, secondary peaks, and achievement of therapeutic MPA levels.
Main Methods:
- 84 kidney transplant recipients on mycophenolate mofetil (MMF) and tacrolimus underwent intensive MPA pharmacokinetic assessment.
- Determined pharmacokinetics of MPA and metabolites, EHR percentage, and number of secondary peaks.
- Studied associations between EHR, secondary peaks, and MPA therapeutic range achievement.
Main Results:
- MPA pharmacokinetics showed high variability in AUC0-12, trough concentrations, and EHR%.
- No significant association was found between EHR% and MPA AUC0-12 or trough levels.
- MPA AUC0-12 and trough were significantly associated with the number of secondary peaks (0, 1, or ≥2).
Conclusions:
- MPA EHR percentage did not correlate with MPA AUC0-12 or trough levels.
- Three distinct patterns of MPA secondary peaks (0, 1, or ≥2) significantly influenced MPA exposure.
- Further studies are needed to link MPA EHR measures with clinical outcomes.
Related Concept Videos
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure
01:16Kidney Transplant III: Nursing Management
01:28Imaging Studies I: Kidney, Ureter, and Bladder Studies
01:45Kidney Structure
01:17Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...