Pharmacokinetics of oral dexamethasone and midazolam when administered with single-dose intravenous 150 mg fosaprepitant in healthy adult subjects.

Abstract:

:Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting. This study evaluated the effect of fosaprepitant 150 mg on CYP3A4 metabolism. Fosaprepitant 150 mg has been submitted to regulatory agencies for consideration of approval as a single-day alternative to the 3-day oral aprepitant antiemetic regimen currently marketed. Part 1 of the study evaluated the drug interaction between fosaprepitant 150 mg and oral dexamethasone (8 mg daily for 3 days). Part 2 of the study evaluated the drug interaction between fosaprepitant 150 mg and oral midazolam (2 mg on days 1 and 4). Thirteen subjects were enrolled in part 1 and 10 in part 2. For dexamethasone, 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. Similarly, for midazolam, fosaprepitant increased the area under the plasma concentration-time curve from 0 hours to infinity by approximately 1.8-fold on day 1 but had no effect on midazolam pharmacokinetics on day 4. Fosaprepitant 150 mg is a weak inhibitor of CYP3A4. Oral dexamethasone doses on days 1 and 2 should be reduced by approximately 50% when coadministered with intravenous fosaprepitant 150 mg on day 1.

journal_name

J Clin Pharmacol

authors

Marbury TC,Ngo PL,Shadle CR,Jin B,Panebianco D,Caro L,Valentine J,Murphy G

doi

10.1177/0091270010387792

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1712-20

issue

12

eissn

0091-2700

issn

1552-4604

pii

0091270010387792

journal_volume

51

pub_type

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