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Effect of Aprepitant on the Pharmacokinetics of Intravenous Midazolam
Author(s) -
Majumdar Anup K.,
Yan Kerri X.,
Selverian Diana V.,
Barlas Suna,
Constanzer Marvin,
Dru James,
McCrea Jacqueline B.,
Ahmed Tuli,
Frick Glen S.,
Kraft Walter K.,
Petty Kevin J.,
Greenberg Howard E.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007300807
Subject(s) - aprepitant , midazolam , antiemetic , medicine , anesthesia , pharmacokinetics , confidence interval , pharmacology , vomiting , sedation
Oral aprepitant 125 mg, an antiemetic and a moderate inhibitor of the metabolism of oral midazolam, was assessed for interaction with intravenous midazolam in 12 subjects randomized to intravenous midazolam 2 mg ± oral aprepitant 125 mg. The hypothesis was that midazolam AUC would not change by more than 2‐fold (consistent with no more than weak inhibition) when midazolam + aprepitant was compared with midazolam alone. An AUC geometric mean ratio (midazolam + aprepitant/midazolam) with 90% confidence interval upper bound ≤2.0 (an increase in midazolam felt to be of modest clinical significance in the highly monitored perioperative period) was prespecified. Aprepitant increased intravenous midazolam AUC 0–∞ 1.47‐fold (90% confidence interval, 1.36–1.59), which fell within the prespecified criterion.