Midazolam (caution): CYP3A4 inhibition. Majumdar 2007 (PMID:17463213) verbatim: "Aprepitant increased intravenous midazolam AUC(0-infinity) 1.47-fold (90% confidence interval, 1.36-1.59)". 12 subjects, randomized, IV midazolam 2 mg ± 125 mg PO aprepitant. AUC 1.47× IV; Ki ≈ 1.5/0.47 = 3.19 µM. Caveat: IV midazolam bypasses gut CYP3A — ORAL midazolam interaction is larger (label cites ~3× AUC). Authored from the abstract-verbatim IV value.
Dexamethasone (caution): CYP3A4 inhibition. Marbury 2011 (PMID:21209230) verbatim: "fosaprepitant increased the area under the plasma concentration-time curve from 0 to 24 hours by approximately 2.0-fold on days 1 and 2 and to a lesser extent (~1.2-fold) on day 3". Caveat: fosaprepitant 150 mg IV (aprepitant prodrug), 8 mg PO dexamethasone × 3d. Peak AUC ratio 2.0×; Ki ≈ 1.5/1.0 = 1.50 µM. Dexamethasone dose halved in aprepitant-containing antiemetic regimens.
Tolbutamide (caution): CYP2C9 INDUCTION direction (polarity flipped from aprepitant's CYP3A4 inhibition of midazolam/dexamethasone). Shadle 2004 (PMID:14973304) verbatim: "The ratio (aprepitant/placebo) of the geometric mean AUC fold-change from baseline for tolbutamide was 0.77 on day 4 (p < 0.01), 0.72 on day 8 (p < 0.001), and 0.85 on day 15 (p = 0.05)". 24 healthy, double-blind, aprepitant 125/80/80 mg × 3d. Day 8 nadir 0.72 → induction_factor 1.39. Transient; recovers by day 15.