Prospective, 6 Month, Open Label, Conversion Study from Mycophenolate Mofetyl to Mycophenolic Acid Evaluating the Severity of Gastro-Intestinal Symptoms and Mycophenolic Acid Urinary Metabolite as a Surrogate Marker of Plasmatic Area Under the Curve
1Nephrology, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada
2Research Center, Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
Meeting: 2015 American Transplant Congress
Abstract number: C68
Keywords: Dosage, Immunosuppression, Kidney transplantation, Pharmacokinetics
Session Information
Session Name: Poster Session C: Immunosuppression/Compliance
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Introduction: Treatment with mycophenolate mofetil (MMF) often results in adverse gastro-intestinal (GI) events, which can lead to dose reductions that in turn can increase the risk of rejection. Mycophenolic acid (MPA) seems to induce fewer GI side effects. Currently, the measurement of 12 hours plasmatic MPA area under the curve (AUC) is the most accurate way to determine MPA exposure in kidney transplant patients. MPA glucuronide (MPAG) is the most abundant metabolite of MPA and its route of elimination is via the urine. The quantity of MPAG in the urine, if shown to correlate with plasma levels of MPA, could serve as a surrogate marker for plasmatic MPA AUC.
Method: Open label single center study of 56 patients receiving MMF at the time of screening. All patients underwent an equimolar conversion to MPA. Patients filled the gastrointestinal symptom rating scale (GSRS) questionnaire at study entry, month 1,3 and 6. Fourteen of the 56 patients were enrolled in the pharmacokinetics sub-study. These patients had 12 hours plasma MPA AUC and 12 hours urine content of MPAG measured by high performance liquid chromatography at month 1 and 3.
Results: 85,2% of the patients could tolerate their initial or a higher dose of MPA during the whole course of the study. The scores of the five syndromes evaluated by the GSRS questionnaire (diarrhea, indigestion, constipation, abdominal pain and reflux) improved as soon as 1 month after the conversion and remained statistically better at 6 months (p<0.0001) when compared with baseline. The correlation between the urinary amount of MPAG excreted in 12 hours and the 12 hours MPA plasma AUC was r=0.82 (p=0.0011) at month 1 and r=0.87 (p=0.0002) at month 3. The correlations remained statistically highly significant when the urinary excretion of MPAG was corrected for the glomerular filtration rate: r=0.93 (p<0.0001)) month 1 and r=0.84 (p=0.0004) month 3. The kidney function and the cell blood counts were stable during the study.
Conclusion: In our study, switching from MMF to MPA to improve GI tolerance was successful and safe in more than 85% of patients. Measuring the urinary excretion of MPAG could be a useful tool in practice to estimate the MPA exposure in kidney transplant recipients.
To cite this abstract in AMA style:
Tran D, Boucher A, Senécal L, Pichette V, Leblond F, Collette S. Prospective, 6 Month, Open Label, Conversion Study from Mycophenolate Mofetyl to Mycophenolic Acid Evaluating the Severity of Gastro-Intestinal Symptoms and Mycophenolic Acid Urinary Metabolite as a Surrogate Marker of Plasmatic Area Under the Curve [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/prospective-6-month-open-label-conversion-study-from-mycophenolate-mofetyl-to-mycophenolic-acid-evaluating-the-severity-of-gastro-intestinal-symptoms-and-mycophenolic-acid-urinary-metabolite-as-a-s/. Accessed May 19, 2025.« Back to 2015 American Transplant Congress