Which of the following immunosuppressants selectively inhibits inosine monophosphate dehydrogenase (IMPDH) and is preferentially used in combination with calcineurin inhibitors?

Explanation

## Mycophenolate Mofetil (MMF): IMPDH Inhibition **Key Point:** Mycophenolate mofetil (MMF) is a selective, non-competitive inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo guanine nucleotide synthesis. **High-Yield:** MMF has selective antiproliferative effects on T and B lymphocytes because: - Lymphocytes depend almost entirely on the de novo pathway for nucleotide synthesis - Non-lymphoid cells can use the salvage pathway (hypoxanthine-guanine phosphoribosyltransferase; HGPRT) - This selectivity minimizes effects on other cell types **Clinical Pearl:** MMF is almost always used in combination with calcineurin inhibitors (tacrolimus or cyclosporine) and corticosteroids in post-transplant regimens because it targets a different pathway and provides synergistic immunosuppression. ### Mechanism MMF (prodrug) → mycophenolic acid (active form) → IMPDH inhibition → ↓ GTP synthesis → ↓ T and B cell proliferation. ### Pharmacokinetics - Oral bioavailability: ~94% - Undergoes enterohepatic recirculation - Metabolized to mycophenolic acid (active) and phenolic glucuronide (inactive) ### Adverse Effects - Gastrointestinal: diarrhea, nausea, abdominal pain (most common) - Bone marrow suppression (leukopenia, anemia) - Increased infection risk - Teratogenic (Category C/D) **Mnemonic:** **MMF = IMPDH** (selective for lymphocyte de novo pathway). [cite:KD Tripathi 8e Ch 75]