| Item |
Information |
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Drug Groups
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approved |
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Description
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Mycophenolic acid is an an immunosuppresant drug and potent anti-proliferative, and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple therapy including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. It is also useful in research for the selection of animal cells that express the E. coli gene coding for XGPRT (xanthine guanine phosphoribosyltransferase). |
| Indication |
For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids. |
| Pharmacology |
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. |
| 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. |
| Affected Organisms |
| • |
Humans and other mammals |
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| Biotransformation |
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. |
| Absorption |
Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95% |
| 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. |
| Protein Binding |
>98% |
| Distribution |
* 54 ± 25 L |
| Clearance |
* 140 +/- 30 mL/min [Stable renal transplant patients] |
| References |
| • |
Woodroffe R, Yao GL, Meads C, Bayliss S, Ready A, Raftery J, Taylor RS: Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study. Health Technol Assess. 2005 May;9(21):1-179, iii-iv.
[Pubmed]
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| External Links |
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