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01-04-2011 | Original Article

Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer

Authors: Uday B. Dandamudi, Laurel M. Adams, Brendan Johnson, John Bauman, Shannon Morris, Sharon Murray, R. Timothy Webb, Elaina Gartner, Raymond Hohl, Lionel D. Lewis

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2011

Abstract

Purpose

The neurokinin-1 receptor antagonist, casopitant, is a weak-to-moderate inhibitor of cytochrome P450 isoenzyme 3A4 (CYP3A) and has the potential to inhibit the metabolism of CYP3A substrates such as docetaxel.

Methods

Fourteen cancer patients were enrolled in this phase 1, open-label, randomized, two-period crossover study. Intravenous (i.v.) docetaxel was coadministered with oral ondansetron and dexamethasone with (Regimen B) or without (Regimen A) 150 mg single-dose oral casopitant.

Results

The geometric least-squares mean Regimen B: Regimen A ratios (90% confidence interval) for docetaxel maximum plasma concentration and area under the concentration–time curve from time 0 extrapolated to infinity were 0.97 (0.83, 1.12) and 1.06 (0.94, 1.19), respectively. Coadministration of casopitant and docetaxel was well tolerated, with adverse event profiles and absolute neutrophil count nadirs similar for both treatments.

Conclusions

C_max and AUC of docetaxel were similar when given as monotherapy or when given in combination with casopitant. Likewise, absolute neutrophil count nadirs were similar for docetaxel alone or docetaxel with casopitant.

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Title: Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer
Authors: Uday B. Dandamudi
Laurel M. Adams
Brendan Johnson
John Bauman
Shannon Morris
Sharon Murray
R. Timothy Webb
Elaina Gartner
Raymond Hohl
Lionel D. Lewis
Publication date: 01-04-2011
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1381-2

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Abstract

Purpose

Methods

Results

Conclusions

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