Itraconazole
Itraconazole. Triazole antifungal — fungal CYP51 inhibitor. Strong CYP3A4 inhibitor + P-glycoprotein inhibitor — major DDI perpetrator (statin… Oral half-life 21 h.
Triazole antifungal — fungal CYP51 inhibitor. Strong CYP3A4 inhibitor + P-glycoprotein inhibitor — major DDI perpetrator (statin myopathy, ergot crisis, sedative oversedation). Highly lipophilic; absorption requires gastric acid + food (capsule) but solution form is enhanced.
PK: the half-life 21 h is verbatim and stands, with a caveat that matters — it is a SINGLE-DOSE CAPSULE terminal value in a drug whose own cited abstract calls its elimination saturable and reports a SEVEN-FOLD exposure accumulation at steady state, so it does not describe repeated dosing. All five references were perpetrator interaction studies containing no itraconazole parameter. V 700 L was APPARENT and was paired with an independent bioavailability, a live double-division; F is now pinned to 1 and the volume re-cited to the published apparent figure of 672 L. F 0.55 IS A DIGIT COLLISION WITH TWO READINGS — an absolute "about 55%" in a review, and a capsule-to-solution RELATIVE ratio of 0.55 — and no scalar is defensible in any case: the capsule delivers barely half of the oral solution, food significantly increases absorption, and the kinetics are explicitly saturable. ACTIVE METABOLITE: hydroxy-itraconazole has comparable in-vitro activity at two to three times the parent concentration, so a parent-only curve understates active exposure roughly three-fold. INTERACTIONS: FIVE OF THE EIGHT AFFINITIES ON THIS RECORD ARE NOT AFFINITIES — they are the published exposure fold-change inverted through one assumed inhibitor concentration of 0.5 µM, and every one of them cites a clinical interaction study rather than any in-vitro measurement. THE CALIBRATION IS SOUND, WHICH IS WHY NOTHING IS DELETED: 0.5 µM is within six percent of this record own modelled mean plasma level, so the solver reproduces each published ratio at typical exposure. What was wrong was the label — a calibration sitting in a field documented as a measurement, against papers a reader would search in vain for a Ki. All five now declare the basis and both inputs, and the lint recomputes the constant. THREE EDGES DO NOT RECONSTRUCT AND ARE LEFT ALONE AND LOGGED: simvastatin, midazolam and cyclosporine imply ratios of 3.9, 4.8 and 1.3 against cited figures of at least tenfold, ten to fifteen fold, and about twofold. They look deliberately ATTENUATED — a tenfold clearance collapse is a violent thing to render — but that is a guess, and an undocumented cap is its own defect.
Pharmacokinetics
- Oral — t½ 21 h · F 100% · Vd 672 L
- IV — t½ 21 h · F 100% · Vd 672 L
Related compounds
- Simvastatin — contraindicated
- Cyclosporine — major
- Midazolam — major
- Triazolam — contraindicated
- Alprazolam — caution
- Atorvastatin — caution
- Lovastatin — contraindicated
- Oxycodone — caution
Sources: PMID:7995001, PMID:9784084, PMID:11061579, PMID:8689812, PMID:20076952, PMID:17048974