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

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.

• 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
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 67 Issue 4 Pg. 783-90 (Apr 2011) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20556613 (Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiemetics
• Antineoplastic Agents
• Cytochrome P-450 CYP3A Inhibitors
• Enzyme Inhibitors
• Neurokinin-1 Receptor Antagonists
• Piperazines
• Piperidines
• Taxoids
• Docetaxel
• casopitant
• Ondansetron
• Dexamethasone
• Cytochrome P-450 CYP3A
• CYP3A4 protein, human

Topics

• Aged
• Aged, 80 and over
• Antiemetics (adverse effects, pharmacology)
• Antineoplastic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Area Under Curve
• Cross-Over Studies
• Cytochrome P-450 CYP3A
• Cytochrome P-450 CYP3A Inhibitors
• Dexamethasone (pharmacology)
• Docetaxel
• Drug Therapy, Combination
• Enzyme Inhibitors (pharmacology)
• Female
• Humans
• Least-Squares Analysis
• Leukocyte Count
• Male
• Middle Aged
• Neoplasms (drug therapy)
• Neurokinin-1 Receptor Antagonists
• Neutrophils (metabolism)
• Ondansetron (pharmacology)
• Piperazines (adverse effects, pharmacology)
• Piperidines (adverse effects, pharmacology)
• Taxoids (adverse effects, pharmacokinetics, therapeutic use)