Action of glucocorticoids to antagonise cisplatin-induced acute and delayed emesis in the ferret
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AbstractCisplatin 5 mg/kg, i.p, induced an acute (day 1) and delayed (days 2 and 3) emetic response in the ferret that was used to investigate the potential anti-emetic activity of several glucocorticoids. Betamethasone (0.3-3 mg/kg, i.p.) reduced the emesis occurring during the initial 0-24-h period by 71.1-99.5% (P < 0.05). The action of methylprednisolone (1.0-10.0 mg/kg, i.p.) and hydrocortisone (1.0-30.0 mg/kg, i.p.) could not be assessed because the controls exhibited weak emetic responses and dexamethasone produced a non-significant 64.0% reduction at 0.3 mg/kg (P > 0.05). However, all glucocorticoids dose-dependently reduced retching + vomiting during the subsequent 24-56-h period. The rank order of anti-emetic potency was betamethasone (ID80 < 0.3 mg/kg) 2 dexamethasone (ID80 = 0.32 mg/kg)> methylprednisolone (ID80 = 0.66 mg/kg) much greater than hydrocortisone (ID80 > 30 mg/kg). Dexamethasone was ineffective to antagonise the retching + vomiting response during the 24-56-h period when the administration was delayed until 24 h post-cisplatin injection. None of the glucocorticoids reduced the retching + vomiting response occurring during the 56-72-h period. In conclusion, the rank order of anti-emetic potency suggests that inflammation, or mediators of inflammation, contribute to the retching + vomiting response induced by cisplatin. (C) 2001 Published by Elsevier Science B.V.
All Author(s) ListSam TSW, Chan SW, Rudd JA, Yeung JHK
Journal nameEuropean Journal of Pharmacology
Volume Number417
Issue Number3
Pages231 - 237
LanguagesEnglish-United Kingdom
Keywordscisplatin; emesis; glucocorticoid
Web of Science Subject CategoriesPharmacology & Pharmacy; PHARMACOLOGY & PHARMACY

Last updated on 2020-30-05 at 00:28