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An interaction of ondansetron and dexamethasone antagonizing cisplatin‐induced acute and delayed emesis in the ferret
Author(s) -
Rudd J.A.,
Naylor R.J.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15388.x
Subject(s) - retching , ondansetron , vomiting , dexamethasone , anesthesia , medicine , antiemetic
1 Cisplatin, 5 mg kg −1 , i.p., administered as a single treatment, 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 ondansetron and dexamethasone and their interaction over a three day period. 2 Ondansetron, 1 mg kg −1 , i.p., administered three times per day in two experiments, antagonized significantly the retching and vomiting that occurred on days 1 and 2 by 60–76 and 73–84%. On the third day of treatment there was a trend for a 38% reduction in one experiment and a 74% reduction in the other. 3 There was a trend for dexamethasone, 1 mg kg −1 , i.p., administered as a single daily injection for three days, to reduce by 37% the retching and vomiting response that occurred on day 1, the reduction of 77% on day 2 achieved significance and dexamethasone non‐significantly increased the retching and vomiting response by 46% on day 3. However, dexamethasone 1 mg kg −1 i.p. administered three times per day for three days significantly reduced the retching+vomiting reponse by 85, 97 and 86% on days 1, 2 and 3 respectively. 4 The combination of dexamethasone, 1 mg kg −1 , i.p., as single daily injections with ondansetron, 1 mg kg −1 , i.p., administered three times per day improved the control of the retching and vomiting response, significantly reducing the total numbers of retches and vomits by more than 70% over a three day period. The combination of dexamethasone (1.0 mg kg −1 ) and ondansetron (1.0 mg kg −1 ), both administered three times daily, abolished cisplatin‐induced emesis over the three day period. 5 The three times per day administration of ondansetron, 1 mg kg −1 , i.p., plus dexamethasone, 1 mg kg −1 , i.p., administered only on day 1 prevented day 1 emesis but did not modify the retching and vomiting that occurred on days 2 and 3. 6 The present results indicate that ondansetron and dexamethasone significantly reduce cisplatininduced emesis in the ferret during both the acute and delayed phase; drug/co‐treatment can exert an additive action to abolish cisplatin‐induced emesis. The ferret model may be useful to detect anti‐emetic drug action for treatment of chemotherapy‐induced acute and delayed emesis in man.