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

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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

Cmax 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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Acknowledgments

Funding for this study was provided by GlaxoSmithKline (NCT00440128). All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Editorial support in the form of editorial suggestions to draft versions of this paper, assembling tables, collating authors comments, copyediting, fact checking, referencing, and graphic services was provided by Publication CONNEXION and was funded by GlaxoSmithKline.

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Authors and Affiliations

  1. Dartmouth Medical School and The Norris Cotton Cancer Center, Lebanon, NH, USA

    Uday B. Dandamudi & Lionel D. Lewis

  2. GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC, 27709, USA

    Laurel M. Adams, Brendan Johnson, John Bauman, Shannon Morris & Sharon Murray

  3. Genesis Cancer Center, Hot Springs, AR, USA

    R. Timothy Webb

  4. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Elaina Gartner

  5. University of Iowa, Iowa City, IA, USA

    Raymond Hohl

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  1. Uday B. Dandamudi
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Correspondence to Laurel M. Adams.

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Dandamudi, U.B., Adams, L.M., Johnson, B. et al. Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer. Cancer Chemother Pharmacol 67, 783–790 (2011). https://doi.org/10.1007/s00280-010-1381-2

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  • DOI: https://doi.org/10.1007/s00280-010-1381-2

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