Tacrolimus

Category: pharmacological

Aliases: FK-506, Prograf, Advagraf

Pharmacological Mechanism

Binds FKBP-12 → inhibits calcineurin → same T-cell IL-2 suppression mechanism as cyclosporine but ~100× more potent per mg. CYP3A4 + P-gp substrate — interaction list as severe as cyclosporine. Displaced cyclosporine as preferred transplant immunosuppressant.

Half-Life (t½)

PO: 12h, IV: 12h

Dosing Guidelines

PO: Typical 0.167 mg (Range: 0.1–0.3 mg)
IV: Typical 0.167 mg (Range: 0.1–0.3 mg)
TD: Typical 0.167 mg (Range: 0.1–0.3 mg)

Target Organ Systems

digestive
immune-hematologic

Interactions

Schisandra (major): Raises tacrolimus AUC 2–3× via CYP3A4 + P-gp inhibition. [Giacomini 2010]
St. John's Wort (contraindicated): CYP3A4 + P-gp induction → sub-therapeutic levels → rejection risk. [Markowitz 2003]

Pathways It Modulates

Calcineurin / NFAT T-cell activation (inhibitor) — calcineurin (via FKBP12)
CD4 T-helper differentiation (inhibitor) — calcineurin (more potent than CsA)
DNA-damage cytotoxic chemotherapy (inhibitor) — calcineurin (via FKBP12 binding)
mTOR signaling (inhibitor) — calcineurin (FKBP12-tacrolimus complex)

Chemical Identifiers

PubChem CID: 445643
Formula: C44H69NO12
Molecular weight: 804.02 g/mol
InChIKey: QJJXYPPXXYFBGM-LFZNUXCKSA-N
SMILES: C[C@@H]1C[C@@H]([C@@H]2[C@H](C[C@H]([C@@](O2)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H]([C@@H]([C@H](CC(=O)[C@@H](/C=C(/C1)\C)CC=C)O)C)/C(=C/[C@@H]4CC[C@H]([C@@H](C4)OC)O)/C)O)C)OC)OC