Action of glucocorticoids to antagonise cisplatin-induced acute and delayed emesis in the ferret.
Cisplatin 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 (ID(80)<0.3 mg/kg)>/=dexamethasone (ID(80)=0.32 mg/kg)>methylprednisolone (ID(80)=0.66 mg/kg)&z.Gt;hydrocortisone (ID(80)>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.
Sam
T S
TS
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Chan
S W
SW
Rudd
J A
JA
Yeung
J H
JH
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000932:Antiemetics / Q000494:pharmacology / Q000627:therapeutic use; D001623:Betamethasone / Q000494:pharmacology; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005289:Ferrets; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy
D000893:Anti-Inflammatory Agents; D000932:Antiemetics; D005938:Glucocorticoids; D003907:Dexamethasone; D001623:Betamethasone; D002945:Cisplatin; D006854:Hydrocortisone; D008775:Methylprednisolone