Collect specimen just prior to next dose (ie, trough)
Correct interpretation requires a trough specimen (just before the next regular dose). Specimens collected at other times in the dosing cycle are likely to have higher mycophenolic acid levels. In these cases, the reference range does not apply.
Mycophenolate mofetil (CellCept) is a new immunosuppressive agent useful in organ transplantation. It is approved for use in renal, hepatic, and cardiac transplants. When mycophenolate mofetil enters the blood, it is immediately metabolized to the active drug, mycophenolic acid (MPA), which inhibits inosine monophosphate dehydrogenase and interferes with the de novo pathway of guanosine nucleotide synthesis selectively in lymphocytes. MPA inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. MPA acts in the same fashion as azathioprine, and MPA is suggested as replacement therapy for azathioprine. The drug is deactivated by the hepatic enzyme, uridine diphosphate glucuronosyltransferase to form mycophenolic acid glucuronide (MPA-G).
The principle clinical problem encountered in MPA therapy is excessive immunosuppression, which predisposes the patient to systemic infection. Measurement of the blood level of MPA and MPA-G can be useful to guide therapy.
Monitoring is recommended before and after making any changes to immunosuppressive therapy or when initiating or discontinuing concomitant medications. Additional monitoring is indicated if the MPA level is not in the therapeutic range or if a major change in health status occurs.
Trough steady-state serum MPA levels over 4.0 mcg/mL indicate that the patient is over-immunosuppressed and susceptible to systemic infections. Decreased dosages may be indicated in these cases.
Low MPA levels and high MPA-G levels suggest that the patient has an active UGT metabolic capability; higher doses may be required to maintain therapeutic levels of MPA. Some patients have a high UGT metabolic capacity. These patients may require 1 gram or more 3 times a day to maintain trough serum MPA levels in the range of 1.0 mcg/mL to 3.5 mcg/mL. They are likely to have MPA-G levels over 100 mcg/mL. MPA-G is inactive; MPA-G levels only describe the patient's metabolic status.
Patients who have low UGT conjugating capability may become over-immunosuppressed, indicated by a trough steady-state serum MPA level over 4.0 mcg/mL and an MPA-G level below 40 mcg/mL. Dose reduction or interval prolongation is indicated in this case.