Tacrolimus
Tacrolimus. Binds FKBP-12 → inhibits calcineurin → same T-cell IL-2 suppression mechanism as cyclosporine but ~100× more potent per mg. CYP3A4 +… Oral half-life 12 h.
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.
PK: F 0.2 is verbatim and stands ("The oral bioavailability was about 20%"). The other values were misattributed: the half-life of 12 h is real but belongs to PMID:8787947, "The mean disposition half-life is 12 hours" — explicitly a disposition value, so route-independence is correct — while the paper it was cited to states 44 h. V 105 L is replaced by 69 L, the steady-state volume of 0.99 L/kg measured in WHOLE BLOOD after intravenous dosing (PMID:9246018). Tacrolimus is the control case for the matrix test and it PASSES: 105 L is 1.5 L/kg, inside the whole-blood range, whereas a plasma-referenced volume would have been roughly fifteen times larger. So it was unsourced, not artefactual. A SINGLE SCALAR BIOAVAILABILITY IS NOT DEFENSIBLE: five verified sources give 14%, about 20%, about 25%, 11 to 19%, and 31 to 49% in bone-marrow transplant patients, a three-and-a-half-fold spread. The transdermal route is removed: topical tacrolimus is an ointment with negligible systemic absorption. A reference on this record contains no tacrolimus at all.
Pharmacokinetics
- Oral — t½ 12 h · F 20% · Vd 69 L
- IV — t½ 12 h · F 100% · Vd 69 L
Related compounds
- Schisandra — major
- St. John's Wort — contraindicated
Sources: PMID:15244495, PMID:20190787, PMID:13129991, PMID:8787947, PMID:9246018