Details

Autor(en) / Beteiligte

• Stoch, S. Aubrey
• Gargano, Cynthia
• Valentine, Jack
• Braun, Matthew P.
• Murphy, M. Gail
• Fedgchin, Margaret
• Majumdar, Anup
• Pequignot, Edward
• Gottesdiener, Keith M.
• Petty, Kevin J.
• Panebianco, Deborah
• Dean, Dennis
• Kraft, Walter K.
• Greenberg, Howard E.

Titel

Double-blind crossover study to assess potential differences in cytochrome P450 3A4 activity in healthy subjects receiving ondansetron plus dexamethasone, with and without aprepitant

Ist Teil von

• Cancer chemotherapy and pharmacology, 2011-06, Vol.67 (6), p.1313-1321

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2011

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• Purpose Because glucocorticoids and the neurokinin-1 receptor antagonist aprepitant influence CYP3A4 activity, this study assessed whether aprepitant added to a 5-HT 3 antagonist and glucocorticoid would affect CYP3A4 induction. Methods In this double-blind, 2-period crossover study, 12 subjects were randomized to receive a triple regimen (oral aprepitant [A] 125 mg, intravenous ondansetron [O] 32 mg, and oral dexamethasone [D] 12 mg day 1; A 80 mg and D 8 mg days 2–3; D 8 mg day 4) in 1 of 2 periods, and a dual regimen (O 32 mg and D 20 mg day 1; D 8 mg bid days 2–4); the D dose was adjusted to account for known dexamethasone/aprepitant interaction. Oral (2 mg) and intravenous (1 mg) stable isotope ( 13 C 5 15 N 1 )–labeled midazolam were simultaneously given as probes on days −1, 6, 8, 15, and 22 of each period. If the a priori 90% confidence interval for the day 6 geometric mean oral midazolam AUC 0–∞ ratio (triple/dual regimen) of fold-change from baseline was above 0.5, it would be concluded that there was no clinically meaningful between-regimen difference in CYP3A4 activity. Results Day 6 oral midazolam AUC 0–∞ geometric mean fold-change from baseline was 0.84 (0.30–1.58 with A, 0.46–1.69 without A). The ratio of geometric mean oral midazolam AUC 0–∞ fold-changes was 1.00 (90% confidence interval 0.80, 1.25). Conclusions Aprepitant plus a 5-HT 3 antagonist and dexamethasone is unlikely to have a significant additional inductive effect on CYP3A4 activity beyond that of the dual regimen.