Cyclosporine
Category: pharmacological
Aliases: Cyclosporin A, Sandimmune, Neoral
Pharmacological Mechanism
Binds cyclophilin → inhibits calcineurin → blocks NFAT dephosphorylation → prevents T-cell IL-2 transcription. CYP3A4 + P-gp substrate — massive interaction list. Narrow therapeutic index; therapeutic drug monitoring mandatory.
Half-Life (t½)
PO: 8h, IV: 8h
Dosing Guidelines
- PO: Typical 6.67 mg (Range: 5–10 mg)
- IV: Typical 6.67 mg (Range: 5–10 mg)
Target Organ Systems
- digestive
- immune-hematologic
Interactions
- St. John's Wort (contraindicated): CYP3A4 + P-gp induction → acute transplant rejection documented. [Markowitz 2003]
- Colchicine (contraindicated): P-gp + CYP3A4 inhibition → fatal colchicine toxicity. [Giacomini 2010]
- Berberine (major): P-gp + CYP3A4 inhibition raises cyclosporine levels. [Giacomini 2010]
- Rosuvastatin (major): OATP1B1 + BCRP transporter inhibition. Simonson 2004 (PMID:15289793): cyclosporine raised rosuvastatin AUC₀₋₂₄ 7.1× and Cmax 10.6× in transplant recipients vs control. Avoid combination — limit alternative statin (or pravastatin/fluvastatin only at low dose).
- Atorvastatin (major): CYP3A4 + OATP1B1 + P-gp inhibition. Lemahieu 2005 (PMID:16095503): cyclosporine significantly raised atorvastatin acid + metabolite exposure in transplant recipients (no fold-change quoted in abstract). Tacrolimus had no effect — distinguishing the OATP1B1 vs CYP3A4 contributions.
Pathways It Modulates
Chemical Identifiers
- PubChem CID: 5284373
- Formula: C62H111N11O12
- Molecular weight: 1202.61 g/mol
- InChIKey: PMATZTZNYRCHOR-CGLBZJNRSA-N
- SMILES: CC[C@H]1C(=O)N(CC(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N([C@H](C(=O)N1)[C@@H]([C@H](C)C/C=C/C)O)C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C
References