Ondansetron

Ondansetron antagonizes the action of serotonin at receptors in the upper gastrointestinal tract and in the chemoreceptor trigger zone of the central nervous system. Given intravenously (IV), it prevents vomiting completely for 24 h in 40% of patients treated with high doses ( 100 mg/m2) of cisplatin and in 70 to 80% of patients treated with 50 to 100 mg/m2 of cisplatin or a combination of cyclophosphamide and doxorubicin. 

Ondansetron is also available in an oral formulation, which can be used for mildly or moderately emetogenic chemotherapy. In one double-blind trial in 318 patients taking combinations of cyclophosphamide with methotrexate and/or doxorubicin, oral ondansetron 1, 4, or 8 mg t.i.d. for 3 d was completely effective in preventing emesis in 57,65, and 66% of patients, respectively, compared to 19% who did not vomit with placebo. 

Ondansetron generally does not cause severe toxicity. Headache and constipation are the most frequent adverse effects. Light-headedness, dizziness, and transient increases in serum aminotransferase activity can occur. Extrapyramidal effects have occurred rarely, and anaphylactoid reactions have been reported. 

How corticosteroids prevent vomiting is unclear, but many studies have confirmed the effectiveness of a single dose of dexamethasone against a variety of anticancer agents. A randomized trial found 

Note Antineoplastics are often given in combination. Dose, route, and schedule of administration also affect the incidence and intensity of nausea and vomiting. 

CAS Registry No. 99614-02-5 (ondansetron), 116002-70-1 (ondansetron), 99614-01-4 (ondansetron hydrochloride dihydrate), 103639-04-9 (ondansetron hydrochloride dihydrate) 

Sample preparation Juice, soft drinks. Iiyect a 10 xL aliquot. Tea. Cool 60 mL tea in an ice bath to about 0° in 1 min. Remove a 10 mL aliquot, add 1 drop concentrated HCl, add 10 mL MeCN, mix, inject a 10 fjiL aliquot. 

Yamreudeewong, W. Danthi, S.N. Hill, R.A. Fox, J.L. Stability of ondansetron hydrochloride injection in various beverages. Am.J.Health-Syst.Pharm., 1995, 52, 2011-2014 

Sample preparation Condition a 1 mL 100 mg cyanopropyl SPE cartridge (J W Scientific) with 2 volumes of MeOH and 2 volumes of water, do not allow to dry. 1 mL Serum + 30 pL 10 pg/mL prazosin in EtOH, vortex for 10 s, add to SPE cartridge, wash with 1 volume MeOH water 10 90, dry under full vacuum for 20 min, elute with four 250 pL aliquots of MeOH triethylamine 999 1. Evaporate the eluate to dryness under a stream of nitrogen at room temperature, dissolve the residue in 250 pL mobile phase, inject a 100 pL aliquot. 

Mobile phase Hexane 95% EtOH isopropanol MeCN 65 25 10 1 

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When ondansetron is administered with rifampin, blood levels of ondansetron may be reduced, decreasing the antiemetic effect. Dimenhydrinate may mask the signs and symptoms of ototoxicity when administered with ototoxic drugp, such as the aminoglycosides (see Chap. 10), causing irreversible hearing damage. When lithium is administered with prochlorperazine, the risk of extrapyramidal reactions increases (see Chap. 32). 

Take granisetron (Kytril), dronabinol (Marinol), or ondansetron (Zofran) before antineoplastic chemodierapy (oral, intravenous) about 30 minutes before the chemodierapy treatment. Take dolasetron mesylate (Anzemet) orally at least 1 hour before... 

Johnson BA, Ait-DaoudN Neuropharmacological treatments for alcoholism scientific basis and clinical findings. Psychopharmacology (Berl) 149 327—344, 2000 Johnson BA, Roache JD, Javors MA, et al Ondansetron for reduction of drinking among biologically predisposed alcoholic patients a randomized controlled trial. 

J Clin Psychopharmacol 23 294-304, 2003a Kranzler HR, Pierucci-Lagha A, Feinn R, et al Effects of ondansetron in early- vs late-onset alcoholics a prospective, open-label study. Alcohol Clin Exp Res 27 1150-1155, 2003b... 

Serotonergic agents Ondansetron, ritanserin, buspirone Large controlled studies are not encouraging. 

Johnson BA, Roache JD, Javors MA, et al Ondansetron for reduction of drinking among biologically predisposed alcoholic patients a randomized controlled trial. 

HT3 Depolarisation Ligand-gated Na+/K+ channel 2-methyl 5-HT Ondansetron Postsynaptic and... 

There have been few attempts to manipulate the monoamines in AzD and those using selegiline, the MOAb inhibitor, have shown little effect although the 5-HT3 antagonist, ondansetron, may give a slight improvement. 

Currently, hopes for compounds with greater clinical efficacy and faster onset of action than buspirone rest on the development of selective ligands for 5-HT receptors. So far, antagonists of 5-HT2a/c (e-g- ritanserin), 5-HTs (e.g. ondansetron) and 5-HT4 (e.g. zacopride) receptors have all been explored but their anti-anxiety effects are, at best, equivocal. Full appraisals of the role of 5-HT systems in anxiety and the actions of anti-anxiety drugs are to be found in Handley (1995), Barnes and Sharp (1999) and Olivier, van Wijngaarden and Soudijn (2000). 

Dextromethorphan, meperidine, and pentazocine ° Amphetamine, fenfluoramine, dexfenfluoramine, methylphenidate, and cocaine ° Sibutramine, St. John s wort, ondansetron, granisetron, dolasetron, and palonosetron... 

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