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Lack of Effect of Aprepitant on Hydrodolasetron Pharmacokinetics in CYP2D6 Extensive and Poor Metabolizers
Author(s) -
Li Susie Xiujiang,
Pequignot Edward,
Panebianco Deborah,
Lupinacci Paul,
Majumdar Anup,
Rosen Laura,
Ahmed Tuli,
Royalty Jane E.,
Rushmore Thomas H.,
Murphy M. Gail,
Petty Kevin J.
Publication year - 2006
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 - 10.1177/0091270006288954
Subject(s) - aprepitant , pharmacokinetics , pharmacology , active metabolite , vomiting , crossover study , antiemetic , cyp3a4 , nausea , medicine , cyp2d6 , bioavailability , anesthesia , alternative medicine , pathology , cytochrome p450 , metabolism , placebo
To prevent chemotherapy‐induced nausea and vomiting, aprepitant is given with a corticosteroid and a 5‐hydroxytryptamine type 3 antagonist, such as dolasetron. Dolasetron is converted to the active metabolite hydrodolasetron, which is cleared largely via CYP2D6. The authors determined whether aprepitant, a moderate CYP3A4 inhibitor, alters hydrodolasetron pharmacokinetics in CYP2D6 poor and extensive metabolizers. Six CYP2D6 poor and 6 extensive metabolizers were randomized in an open‐label, crossover fashion to treatment A (dolasetron 100 mg on day 1) and treatment B (dolasetron 100 mg plus aprepitant 125 mg on day 1, aprepitant 80 mg on days 2–3). For hydrodolasetron area under the concentration‐versus‐time curve (AUC 0‐∞ ) and peak plasma concentration (C max ), geometric mean ratios (B/A) and 90% confidence intervals (CIs) fell below the predefined limit (≤2.0) for clinical significance (AUC 0‐∞ , 1.09 [90% CI, 1.01–1.18], C max , 1.08 [90% CI, 0.94–1.24]). Aprepitant did not affect the pharmacokinetics of hydrodolasetron, regardless of CYP2D6 metabolizer type, and was generally well tolerated when coadministered with dolasetron in volunteers.