We evaluated the safety and efficacy of
RS-25259, a potent and long-acting selective
5-HT3 receptor antagonist, for the prevention of
postoperative nausea and vomiting (
PONV) in women undergoing
hysterectomy procedures. In this randomized, double-blind, placebo controlled, dose-ranging study, 218 healthy, consenting women were assigned to one of the six treatment groups: placebo or
RS-25259 0.1, 0.3, 1.0, 3.0, or 30 microg/kg. All patients underwent a standardized
general anesthetic technique. The study medication was administered i.v. 20-30 min before the end of surgery. During the initial 24-h period after surgery, the incidence of
vomiting, the need for rescue
antiemetics, the time to the first episode of
emesis, and administration of rescue
antiemetic medication, as well as a
nausea visual analog scale and verbal categorical scale scores were recorded. In addition, recovery times from the end of
anesthesia and the incidences of perioperative side effects were noted. Only 30 microg/kg
RS-25259 significantly decreased the incidence of
vomiting and the requirement for rescue
antiemetics. The largest dose of
RS-25259 also delayed the time to the first
emetic episode and reduced the number of treatment failures. However, no differences were found in the severity of
postoperative nausea (versus saline), and postoperative
headaches were more common after the administration of
RS-25259 0.3-30 microg/kg i.v. In conclusion,
RS-25259 30 microg/kg i.v. was effective in reducing the incidence of
PONV after major
gynecologic surgery, but the occurrence of
headaches with the larger doses of
RS-25259 is a concern.
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