Collect specimen just prior to next dose (ie, trough)
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 immediately after transplant up to 3 weeks after therapy is initiated to evaluate dosing adequacy. Additional monitoring is indicated if the MPA level is not in the therapeutic range or if a major change in health status occurs.
Trough serum levels of mycophenolic acid (MPA) at steady-state (>2 weeks at the same dose) in the range of 1.0 to 3.5 mcg/mL indicate adequate therapy. Mycophenolic acid glucuronide (MPA-G) levels in the range of 35 to 100 mcg/mL indicate that the patient has normal uridine diphosphate glucuronosyltransferase (UGT) metabolic capacity. MPA-G levels are typically in the range of 100 to 250 mcg/mL during the 2 weeks following transplantation. MPA-G typically decreases after this initial post-transplant phase.
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 a MPA-G level below 40 mcg/mL. Dose reduction or interval prolongation is indicated in this case.