Lack of effect of aprepitant on hydrodolasetron pharmacokinetics in CYP2D6 extensive and poor metabolizers.
J Clin Pharmacol
; 46(7): 792-801, 2006 Jul.
Article
in En
| MEDLINE
| ID: mdl-16809805
ABSTRACT
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 (AUC0-infinity) and peak plasma concentration (Cmax), geometric mean ratios (B/A) and 90% confidence intervals (CIs) fell below the predefined limit (2.0) for clinical significance (AUC0-infinity, 1.09 [90% CI, 1.01-1.18], Cmax, 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinolizines
/
Serotonin Antagonists
/
Morpholines
/
Cytochrome P-450 CYP2D6
/
Indoles
/
Antiemetics
Type of study:
Clinical_trials
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Clin Pharmacol
Year:
2006
Document type:
Article
Affiliation country:
United States