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First published on April 26, 2007, doi:10.1177/0091270007300807

The Journal of Clinical Pharmacology 2007;47:744.

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©© 2007 American College of Clinical Pharmacology, Inc.
The Journal of Clinical Pharmacology , 10.1177/0091270007300807

Article

Effect of Aprepitant on the Pharmacokinetics of Intravenous Midazolam

Anup K. Majumdar 1, Kerri X. Yan 1, Diana V. Selverian 1, Suna Barlas 1, Marvin Constanzer 1, James Dru 1, Jacqueline B. McCrea 1*, Tuli Ahmed 1, Glen S. Frick 2, Walter K. Kraft 2, Kevin J. Petty 1, and Howard E. Greenberg 2

1 Merck Research Laboratories, West Point, Pennsylvania
2 Thomas Jefferson University, Philadelphia, Pennsylvania

* To whom correspondence should be addressed. E-mail: jackie_mccrea{at}merck.com.


  Abstract
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 AUC0-{infty} 1.47-fold (90% confidence interval, 1.36-1.59), which fell within the prespecified criterion.
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