We compared the efficacy and safety of ondansetron (GR 38032F), a selective antagonist of serotonin S3 receptors, with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer. The patients received either three intravenous doses of ondansetron (0.15 mg per kilogram of body weight) or normal saline (placebo) at four-hour intervals, beginning 30 minutes before the administration of cisplatin. Nausea and vomiting were markedly diminished in the group given ondansetron. The median time to the first episode of emesis was 2.8 hours in the placebo group and 11.6 hours in the ondansetron group (P less than 0.001); the median number of episodes in 24 hours was 5.5 in the placebo group and 1.5 in the ondansetron group (P less than 0.001); the mean (+/- SEM) number of regurgitations or dry heaves per episode was 3.2 +/- 0.5 in the placebo group and 1.17 +/- 0.1 in the ondansetron group (P less than 0.001). None of the 14 patients given ondansetron, but 12 of 14 given placebo, required treatment with antiemetic-rescue agents for the control of nausea and vomiting. There were no adverse effects attributable to ondansetron. The urinary excretion of 5-hydroxyindoleacetic acid, the main metabolite of serotonin, was increased in all patients two to six hours after they received cisplatin chemotherapy, and the increases paralleled the episodes of emesis. We conclude that ondansetron is an effective and safe agent for controlling the nausea and vomiting induced by cisplatin treatment. We suggest that cisplatin treatment increases the release of serotonin from enterochromaffin cells, and that ondansetron acts by blocking S3 receptors for serotonin.
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Department of Pharmacology, University of North Carolina, Chapel Hill.
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[Full Text]
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[Abstract][Full Text]
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[Abstract][Full Text]
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334: 1106-1115
[Full Text]
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331: 394-398
[Full Text]
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154: 1733-1740
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329: 1790-1796
[Full Text]
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116: 1001-1008
[Abstract]
Durivage, H. J., Burnham, N. L.
(1991). Prevention and Management of Toxicities Associated With Antineoplastic Drugs. Journal of Pharmacy Practice
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(1990). NEW POWERFUL ANTIEMETICS: SEROTONIN-RECEPTOR BLOCKERS. JWatch General
1990: 2-2
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