| Indication |
For the prophylaxis of organ rejection in patients receiving
allogeneic renal transplants, administered in combination with
cyclosporine and corticosteroids. |
| Pharmacodynamics |
Mycophenolic acid is an antibiotic substance derived from Penicillium stoloniferum.
It blocks de novo biosynthesis of purine nucleotides by inhibition of
the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is
important because of its selective effects on the immune system. It
prevents the proliferation of T-cells, lymphocytes, and the formation of
antibodies from B-cells. It also may inhibit recruitment of leukocytes
to inflammatory sites. |
| Mechanism of action |
Mycophenolic acid is a potent, selective, uncompetitive, and
reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and
therefore inhibits the de novo pathway of guanosine nucleotide
synthesis without incorporation into DNA. Because T- and B-lymphocytes
are critically dependent for their proliferation on de novo synthesis of
purines, whereas other cell types can utilize salvage pathways,
mycophenolic acid has potent cytostatic effects on lymphocytes.
Mycophenolic acid inhibits proliferative responses of T- and
B-lymphocytes to both mitogenic and allospecific stimulation. Addition
of guanosine or deoxyguanosine reverses the cytostatic effects of
mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses
antibody formation by B-lymphocytes. Mycophenolic acid prevents the
glycosylation of lymphocyte and monocyte glycoproteins that are involved
in intercellular adhesion to endothelial cells and may inhibit
recruitment of leukocytes into sites of inflammation and graft
rejection. |
| Absorption |
Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95% |
| Volume of distribution |
|
| Protein binding |
>98% |
| Metabolism |
Mycophenolic acid is metabolized mainly by glucuronyl
transferase to glucuronidated metabolites, predominantly the phenolic
glucuronide, mycophenolic acid glucuronide (MPAG). MPAG does not
manifest pharmacological activity. The acyl glucuronide minor metabolite
has pharmacological activity similar to mycophenolic acid. The AUC
ratio of Mycophenolic acid:MPAG:acyl glucuronide is approximately
1:24:0.28 at steady state. |
| Route of elimination |
Not Available |
| Half life |
The mean elimination half-life for mycophenolic acid ranges from
8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours. |
| Clearance |
- 140 +/- 30 mL/min [Stable renal transplant patients]
|
| Toxicity |
Oral (LD50): Acute: 352 mg/kg [Rat], 1000 mg/kg [Mouse], and
>6000 mg/kg [Rabbit]. Possible signs and symptoms of acute overdose
could include the following: hematological abnormalities such as
leukopenia and neutropenia, and gastrointestinal symptoms such as
abdominal pain, diarrhea, nausea and vomiting, and dyspepsia. |
