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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)783-790
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number4
DOIs
StatePublished - Apr 1 2011

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docetaxel
Pharmacokinetics
Neoplasms
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System
Isoenzymes
Neutrophils
Neurokinin-1 Receptor Antagonists
Neurokinin-1 Receptors
Ondansetron
casopitant
Least-Squares Analysis
Metabolism
Cross-Over Studies
Dexamethasone
Area Under Curve
Labels

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Dandamudi, U. B., Adams, L. M., Johnson, B., Bauman, J., Morris, S., Murray, S., ... Lewis, L. D. (2011). Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer. Cancer Chemotherapy and Pharmacology, 67(4), 783-790. https://doi.org/10.1007/s00280-010-1381-2
Dandamudi, Uday B. ; Adams, Laurel M. ; Johnson, Brendan ; Bauman, John ; Morris, Shannon ; Murray, Sharon ; Webb, R. Timothy ; Gartner, Elaina ; Hohl, Raymond ; Lewis, Lionel D. / Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 67, No. 4. pp. 783-790.
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Dandamudi, UB, Adams, LM, Johnson, B, Bauman, J, Morris, S, Murray, S, Webb, RT, Gartner, E, Hohl, R & Lewis, LD 2011, 'Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer', Cancer Chemotherapy and Pharmacology, vol. 67, no. 4, pp. 783-790. https://doi.org/10.1007/s00280-010-1381-2

Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer. / Dandamudi, Uday B.; Adams, Laurel M.; Johnson, Brendan; Bauman, John; Morris, Shannon; Murray, Sharon; Webb, R. Timothy; Gartner, Elaina; Hohl, Raymond; Lewis, Lionel D.

In: Cancer Chemotherapy and Pharmacology, Vol. 67, No. 4, 01.04.2011, p. 783-790.

Research output: Contribution to journalArticle

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T1 - Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer

AU - Dandamudi, Uday B.

AU - Adams, Laurel M.

AU - Johnson, Brendan

AU - Bauman, John

AU - Morris, Shannon

AU - Murray, Sharon

AU - Webb, R. Timothy

AU - Gartner, Elaina

AU - Hohl, Raymond

AU - Lewis, Lionel D.

PY - 2011/4/1

Y1 - 2011/4/1

N2 - 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.

AB - 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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