Effects of granisetron and its combination with dexamethasone on cisplatin-induced delayed emesis in the ferret.
1. Granisetron and its combination with dexamethasone for the treatment of delayed emesis following cisplatin (CDDP) administration were investigated using ferrets. 2. CDDP-induced emesis was significantly inhibited in both the granisetron group and the combined granisetron and dexamethasone group during the acute and delayed phase in terms of total emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly increased as compared with the CDDP control group. 4. 5-Hydroxytryptamine (5-HT) level was increased in the ileum and the 5-hydroxyindole acetic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemetic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination with dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase.
Fukunaka
N
N
Department of Obstetrics and Gynecology, Sapporo Medical University, School of Medicine, Japan.
Sagae
S
S
Kudo
R
R
Endo
T
T
Hirafuji
M
M
Minami
M
M
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000633:toxicity*; D003401:Creatine / Q000097:blood; D003672:Defecation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects; D005289:Ferrets; D017829:Granisetron / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000097:blood; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012964:Sodium / Q000097:blood; D013997:Time Factors; D014554:Urination / Q000187:drug effects; D014839:Vomiting / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D002945:Cisplatin; D003401:Creatine; D003907:Dexamethasone; D017829:Granisetron; D006897:Hydroxyindoleacetic Acid; D011188:Potassium; D012701:Serotonin; D012702:Serotonin Antagonists; D012964:Sodium