[Delayed emesis induced by the chemotherapeutic agent doxorubicin hydrochloride in dogs].
The occurrence of delayed emesis induced 24 h after the administration of a non-platina chemotherapeutic agent, doxorubicin hydrochloride (doxorubicin), as well as behaviors such as feeding, drinking and defecation were examined in dogs. A single intravenous administration of 2 mg/kg doxorubicin induced emesis within 24 h of administration in some dogs, while delayed emesis was observed 24 h after administration in all dogs. This delayed emesis emerged strongly at day 3 or 4 and decreased at day 5. Hypophagia, the decreased frequency of drinking and the increased frequency of defecation were induced shortly after delayed emesis. Twenty-four hours after the administration of doxorubicin, a daily dose of 0.3 and 1 mg/kg/day, p.o. azasetron, a 5-HT3 antagonist, was administered for 4 days. Doxorubicin-induced delayed emesis was observed to decrease by about 30 and 50%, respectively. This result suggests that 5-HT3 receptors play a role in the mechanism of delayed emesis. Azasetron was found to improve the increased frequency of defecation, but exerted no obvious effect on hypophagia or on the decreased frequency of drinking. Taken together, we suggest that doxorubicin-induced emesis in dogs is a useful method to study further the mechanisms of delayed emesis and to investigate novel therapeutic agents against delayed emesis.
Haga
K
K
Drug Development Laboratories, Welfide Corporation, 955, Koiwai, Yoshitomi-cho, Chikujo-gun, Fukuoka 871-8550, Japan. haga-keiichiro@yoshitomi.co.jp
Inaba
K
K
Syoji
H
H
Hashimoto
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology / Q000627:therapeutic use; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004317:Doxorubicin / Q000009:adverse effects*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D008297:Male; D010078:Oxazines / Q000494:pharmacology / Q000627:therapeutic use; D011930:Reaction Time; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C070671:azasetron; D004317:Doxorubicin