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Ondansetron--the first of a new class of antiemetic agents

Ondansetron--the first of a new class of antiemetic agents

Clinical Pharmacy 10(6): 430-446

The chemistry, pharmacokinetics, adverse effects, stability, compatibility, and dosage of ondansetron hydrochloride are described, and clinical studies of the use of ondansetron for the prophylaxis of nausea and vomiting induced by antineoplastic therapy are reviewed. Ondansetron hydrochloride is a specific antagonist of serotonin type 3 (5-HT3) receptors, both in the chemoreceptor trigger zone and in the GI tract. Peak plasma concentrations of ondansetron occur approximately one hour after an oral dose and 6 to 20 minutes after an i.v. dose. The mean elimination half-life is approximately 3.5 hours in healthy volunteers, but it is extended in elderly patients (mean of 7.9 hours). In clinical trials, ondansetron has been shown to provide excellent control of nausea and vomiting in patients treated with cisplatin. Comparisons of ondansetron with metoclopramide in patients treated with various types of chemotherapy have shown better response rates with ondansetron. Ondansetron has also been shown to be effective in controlling nausea and vomiting in patients receiving cyclophosphamide with an anthracycline and in patients receiving combination therapy with cyclophosphamide, methotrexate, and fluorouracil. Adverse effects appear to be mild and include headache, constipation, diarrhea and transient abnormalities in liver function tests. The dose of ondansetron (as the hydrochloride salt) for the prophylaxis of chemotherapy-induced nausea and vomiting in adults is 0.15 mg/kg i.v. every four hours for three doses, beginning 30 minutes before antineoplastic therapy. The efficacy of ondansetron is comparable to that of metoclopramide, and the adverse-effect profile is much less problematic. The cost of ondansetron is much higher than that of metoclopramide; thus its use should be limited to patients at high risk for metoclopramide-induced adverse effects and patients in whom metoclopramide is ineffective.

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Accession: 040864778

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PMID: 1829668

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