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Clinical Trial
. 2009 Sep;17(9):1177-85.
doi: 10.1007/s00520-008-0571-5. Epub 2009 Feb 10.

Impact of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of ondansetron and dexamethasone

Brendan Johnson  1 , Laurel Adams, Emily Lu, Ke Zhang, Peter Lebowitz, Christian Lates, Robert Blum
Affiliations
Clinical Trial

Impact of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of ondansetron and dexamethasone

Brendan Johnson et al. Support Care Cancer. 2009 Sep.

Abstract

Introduction: Pharmacokinetic interactions between casopitant (a substrate and weak to moderate inhibitor of CYP3A), dexamethasone (a substrate and weak inducer of CYP3A), and ondansetron (a mixed CYP substrate) were evaluated in a two-part, three-period, single-sequence study in two groups of healthy subjects.

Materials and methods: Part 1: subjects received oral casopitant (regimen A); oral dexamethasone and IV ondansetron (regimen B); and oral casopitant, a reduced dose of oral dexamethasone, and IV ondansetron (regimen C). Part 2: subjects received oral casopitant (regimen D); IV dexamethasone and oral ondansetron (regimen E); and oral casopitant, IV dexamethasone, and oral ondansetron (regimen F). Each regimen was separated by 14 days.

Results: Casopitant AUC in regimen C was increased 28% on day 1 but decreased 34% on day 3 compared to casopitant alone in regimen A. When given with casopitant and ondansetron in regimen C, dexamethasone AUC was 17% lower on day 1, but similar on day 3, compared to regimen B (representing dose-normalized increases in exposure of 39% and 108%, respectively). Ondansetron exposure was equivalent in regimens B and C. Casopitant AUC in regimen F was similar to regimen D on days 1 and 3. Dexamethasone AUC increased 21% when given with oral casopitant and oral ondansetron (regimen F compared to regimen E). Ondansetron exposure was equivalent in regimens E and F.

Conclusion: When repeat-dose oral dexamethasone is to be coadministered with oral casopitant, a reduction in dexamethasone dose may be considered; however, no change in casopitant dose is required. Ondansetron exposure was not affected by coadministration with casopitant.

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Figures

Fig. 1
Fig. 1
Changes in individual casopitant (top), dexamethasone (middle), and ondansetron (bottom) AUC parameters after administration of casopitant alone, dexamethasone + ondansetron, and casopitant + dexamethasone + ondansetron, from part 1 (HEC regimen)
Fig. 2
Fig. 2
Changes in individual casopitant (top), dexamethasone (middle), and ondansetron (bottom) AUC parameters after administration of casopitant alone, dexamethasone + ondansetron, and casopitant + dexamethasone + ondansetron, from part 2 (MEC regimen)
See this image and copyright information in PMC

References

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