Ipecacuanha-induced emesis: a human model for testing antiemetic drug activity.
In a double-blind, randomized, parallel-group study, five groups of 10 healthy men received single 5-minute infusions of 8 mg, 4 mg, 1 mg, 0.25 mg, or 0.1 mg ondansetron (as hydrochloride dihydrate) 30 minutes before oral administration of 30 ml syrup of ipecacuanha. Emetic episodes and nausea (100 mm visual analog scale) were assessed over an 8-hour period. There were no emetic episodes after 8 or 4 mg ondansetron. Seven, nine, and 10 subjects vomited after 1 mg, 0.25 mg and 0.1 mg ondansetron, respectively, with median times to onset of 62, 31, and 37 minutes. Median peak nausea scores were 0 mm for both 8 and 4 mg ondansetron and 30, 53, and 26 mm for 1, 0.25, and 0.1 mg ondansetron. Adverse events were mild. This model showed a close correlation with clinically effective doses of ondansetron. It may be successfully and safely used to assess the antiemetic potential of 5-HT3-receptor antagonists in healthy subjects.
Minton
N
N
Clinical Pharmacology Division, Glaxo Group Research Ltd., Greenford, Middlesex, England.
Swift
R
R
Lawlor
C
C
Mant
T
T
Henry
J
J
D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007486:Ipecac / Q000037:antagonists & inhibitors*; D008297:Male; D009325:Nausea / Q000517:prevention & control; D017294:Ondansetron / Q000494:pharmacology*; D012016:Reference Values; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D017294:Ondansetron; D007486:Ipecac