From the Guidelines
CellCept (mycophenolate mofetil) works by suppressing the immune system to prevent organ rejection in transplant patients and treat certain autoimmune disorders. It specifically inhibits an enzyme called inosine monophosphate dehydrogenase (IMPDH), which is crucial for the production of guanosine nucleotides needed for DNA synthesis in T and B lymphocytes, as reported in a study published in the Journal of Hepatology in 2016 1. By blocking this pathway, CellCept selectively inhibits the proliferation of these immune cells, which are responsible for attacking transplanted organs or healthy tissues in autoimmune conditions. The mechanism of action of CellCept is further supported by a study published in the Journal of the National Comprehensive Cancer Network in 2020, which highlights its role in inducing apoptosis in lymphocytes through inhibition of the de novo synthesis of purines 1. Some key points to consider when using CellCept include:
- The typical dose ranges from 1-3 grams daily, divided into two doses, though this varies based on the specific condition being treated and patient factors.
- Patients should be monitored regularly for side effects including gastrointestinal issues, increased risk of infections, and potential blood disorders.
- The medication should be taken consistently at the same times each day with or without food.
- Patients should avoid pregnancy while on this medication due to risks of birth defects. It is essential to note that the use of CellCept should be guided by the most recent and highest quality evidence, and patients should be closely monitored for any adverse effects.
From the FDA Drug Label
Mycophenolate mofetil is rapidly absorbed following oral administration and hydrolyzed to form MPA, which is the active metabolite MPA is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novopathway of guanosine nucleotide synthesis without incorporation into DNA Because T- and B-lymphocytes are critically dependent for their proliferation on de novosynthesis of purines, whereas other cell types can utilize salvage pathways, MPA has potent cytostatic effects on lymphocytes.
Mycophenolate mofetil, also known as CellCept, works by inhibiting the de novo pathway of guanosine nucleotide synthesis. This is achieved through its active metabolite, MPA, which is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). As a result, MPA has cytostatic effects on lymphocytes, particularly T- and B-lymphocytes, which are dependent on de novo purine synthesis for their proliferation. This leads to a suppression of the immune response, making it useful for preventing graft rejection in transplant patients 2.
- Key mechanism: Inhibition of IMPDH and de novo guanosine nucleotide synthesis
- Effect on lymphocytes: Cytostatic effects, preventing proliferation and suppressing immune response
- Clinical use: Prevention of graft rejection in transplant patients 2
From the Research
Mechanism of Action
- CellCept (Mycophenolate Mofetil) is a prodrug of mycophenolic acid (MPA), which inhibits inosine monophosphate dehydrogenase (IMPDH) 3, 4, 5, 6.
- IMPDH is a key enzyme in the de novo synthesis of guanosine nucleotides, which are essential for the proliferation of T- and B-lymphocytes 3, 4, 5, 6.
- MPA has a more potent cytostatic effect on lymphocytes than on other cell types, making it an effective immunosuppressive agent 3.
Effects on Lymphocytes
- CellCept suppresses T-lymphocytic responses to allogeneic cells and other antigens 3.
- The drug also suppresses primary, but not secondary, antibody responses 3.
- MPA can induce apoptosis of activated T-lymphocytes, which may eliminate clones of cells responding to antigenic stimulation 3.
Anti-Inflammatory Activity
- MPA inhibits the glycosylation and expression of adhesion molecules, and the recruitment of lymphocytes and monocytes into sites of inflammation 3, 5.
- MPA depletes tetrahydrobiopterin and decreases the production of nitric oxide by inducible NO synthase, which reduces tissue damage mediated by peroxynitrite 3, 5.