Wednesday May 03, 2023 - 09:20 to 10:10
A case study supporting the use of AUC0-12 for therapeutic drug monitoring of mycophenolic acid following liver transplantation
Claudia Beck1, Matthew R McIntyre1, Dennis G Hooper1, Shannan Tujios2.
1R&D, Realtime Laboratories, Carrollton, TX, United States; 2Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, United States
A 72-year old male liver transplant recipient experienced side effects indicating over-suppression of the immune system during routine testing 2 months after transplantation. The patient’s immunosuppressant protocol at the time of testing was 500 mg mycophenolate mofetil (CellCept) twice daily and 3 mg tacrolimus daily. Mycophenolic acid is not tested by the treatment facility. The protocol of the treatment facility is one mycophenolic acid trough concentration directly following transplantation with no further monitoring. Tacrolimus is tested weekly by the treatment facility. The patience was experiencing the following side effects: fluid retention on lower extremities, itching, cough, headache, tremors, unusual hematomas on upper extremities, low absolute neutrophil count, and anemia. It was suggested by the treatment physician to lower the CellCept dose.
MPA levels were tested to further investigate the side effects. The lab result for the trough, or steady state, concentration of MPA was 4.09 ug/mL, which is above the therapeutic range of 1-3.5 ug/mL. This result would usually trigger physicians to decrease the mycophenolic acid dosage under the assumption that it is causing the patient’s immune system to be over-suppressed. The patient was also tested to obtain an AUC0-12 value, which was determined to be 35.77 mg*hr/L by testing 7 specimens collected prior to, and at designated intervals between 0 and 12 hours after administration of CellCept. This value is on the lower end of the reference range for an AUC0-12 value for MPA which spans from 30-60 mg*hr/L. This case indicates that due to differences between individual patient metabolisms a steady state concentration for MPA can at times fail to accurately predict the level of immunosuppression in organ transplant recipients. The case also illuminates the utility of performing AUC0-12 testing for MPA to more accurately understand a patient’s individual metabolism of the drug prior to adjusting dosages to levels that could prove sub-therapeutic.
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