Trough mycophenolate levels are a relatively poor predictor of exposure. A limited sampling strategy combining 4 concentration measurements within the dosing interval (Pre-dose, +1hr, +2 hr, +4hr post dose), allows the calculation of MPA AUC 0–12h the preferred method to assess mycophenolate exposure.
Mycophenolic acid glucuronide levels are also available upon request.
Method: LC-MS/MS
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Mycophenolic acid is available in Australia as mycophenolate mofetil (MMF) and as enteric coated mycophenolate sodium (EC-MPS). In the Alfred pathology service we use LC tandem MS to determine the levels of mycophenolate (MPA). The mechanism of action of MPA includes the inhibition of inosine monophosphate dehydrogenase leading to decreased formation of guanosine monophosphate and selective inhibition of the proliferation of B and T lymphocytes.
MPA area under the curve is determined by limited sampling strategies using serial samples. This method is widely used and there are data correlating levels with outcome of organ transplantation. (1). However, some publications (2) show correlation of trough levels with clinical outcome in renal transplantation.
MPA shows non-linear absorption kinetics. It has enterohepatic circulation, variation in plasma protein binding and variation caused by genetic differences as well as drug-drug interactions. In blood MPA circulates mainly bound to albumin (97 to 99%). Metabolism occurs through the uridine glucuronosyltransferase system (UGT). MPA is glucuronidated into an inactive (MPA 7–O– glucuronide – MPAG) and the pharmacologically active AcMPAG (acyl-glucuronide). The main elimination of MPA is via the renal excretion of the glucuronide with an elimination half-life of 8 to 16 hours.
Trough level of MPA are lowered by concurrent administration of cyclosporine, while co-administration of Tacrolimus increases the concentration of MPA by inhibiting the UDP –glucuronosyltransferase.
While the limited sampling strategy is the preferred method 2 determine MPA area under the curve (AUC) it needs to be stated that the use of EC MPA leads to a larger number of patients where the strategy does not give a meaningful result.
Recommended Levels for AUC0-12h:
In line with international consensus (1) we recommend a target MPA AUC0-12h of 30 to 60 mg*h/L for kidney transplant recipients.
In heart transplantation recipients treated with MMF, calcineurin inhibitors and steroids, MPA AUC0-12h > 36 mg*h/L or C0 greater 2 mg/L is recommended.
1. Bergan S, Brunet M, Hesselink DA, et al. Personalized Therapy for Mycophenolate: Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 2021 Apr 1;43(2):150-200. doi: 10.1097/FTD.0000000000000871. PMID: 33711005 Review.
2. Rhu J, Lee KW, Park H, Park JB, Kim SJ, Choi GS. Clinical Implication of Mycophenolic Acid Trough Concentration Monitoring in Kidney Transplant Patients on a Tacrolimus Triple Maintenance Regimen: A Single-Center Experience. Ann Transplant. 2017 Nov 28;22:707-718. doi: 10.12659/aot.906041.
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