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Ondansetron

Therapeutic Use as an Antiemetic

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Summary

Synopsis

Ondansetron (GR 38032F) is a highly selective 5- HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24- hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the ‘moderate’ doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatintreated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available.

Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics.

Pharmacodynamic Properties

Ondansetron is a new carbazole which blocks serotoninergic neurotransmission at serotonin3 (5-HT3) receptors. It is a potent, highly selective and competitive antagonist of the depolarising effects of serotonin in the rat and rabbit isolated vagus nerve and the rat superior cervical ganglion. Ondansetron blocks the depolarising effect of the 5-HT3-selective agonist 2-methyl-5-HT in longitudinal smooth muscle of guinea-pig ileum, and the Bezold-Jarisch reflex response to 2-methyl-5-HT in anaesthetised rats and cats, but has little effect on 5-HT1 and 5-HT2 mediated responses or on α1, β1 muscarinic, nicotinic, histamine1, histamine2 or GABAa receptors. In vitro, it is at least 70 times more potent than metoclopramide at peripheral 5-HT3 receptors, but has no effect on stereotyped movements induced by dopamine agonists.

In animal models parenterally administered ondansetron reduces the incidence of emetic episodes induced by radiation, cyclophosphamide and cisplatin-based chemotherapies. Since both radiation and cisplatin may release serotonin from chromaffin cells in the intestinal mucosa, and since serotonin activates vagal and possibly splanchnic afferent nerves which in turn reflexly induce nausea and vomiting, it has been proposed that ondansetron acts by blocking serotonininduced depolarisation of vagal afferent nerves. It may also block serotoninergic action in the chemoreceptor trigger zone in the area postrema and the nucleus tractus solitarius of the brainstem, which contain 5-HT3 binding sites probably located on vagal afferent nerve terminals. Ondansetron may slow colonie transit times but this effect is unrelated to its antiemetic action. It has no effect on motion sickness or on emesis induced by dopamine receptor agonists.

Pharmacokinetic Properties

Ondansetron can be administered either intravenously or orally. Following oral administration of ondansetron 8mg, peak plasma concentrations of about 30 µg/L are reached in 1 to 1.5 hours. Orally administered ondansetron is about 60% bioavailable in healthy subjects and about 75% bound to plasma proteins. The apparent volume of distribution is large (160L) and the mean elimination half-life is 3 hours. The clearance of ondansetron may be lower in the elderly. In healthy subjects 60% of a single intravenous radiolabelled dose is eliminated by the kidneys and 25% in faeces, mostly as metabolites. Clinically relevant metabolites have not been reported.

Therapeutic Use

Most clinical trials have studied the control of vomiting over the first 24 hours following chemotherapy. Ondansetron has been given either intravenously (IV) or orally, as a loading dose within the first 30 minutes IV or 1 to 2 hours orally prior to chemotherapy, followed by continuous infusion or by 2 or 3 oral or intravenous doses at intervals of 2 to 8 hours.

In a moderate size noncomparative study ondansetron (0.18 mg/kg intravenously 6- or 8-hourly) completely controlled acute vomiting induced by cisplatin-based chemotherapy in 55% of patients, and reduced the number of emetic episodes to fewer than 3 in a further 20% of patients. Ondansetron delayed the onset of emesis from a median of 2.8 hours with placebo to a median of 11.6 hours after administration of cisplatin, and reduced the incidence of emetic episodes 4-fold and the incidence of retching 3-fold during the 24 hours after administration. No cisplatin-treated patients receiving ondansetron required rescue antiemetic therapy compared with 12 of 14 receiving placebo.

Compared with metoclopramide in several studies, including 4 double-blind crossover trials, ondansetron was more effective in ameliorating nausea and vomiting on the day of chemotherapy. In the largest trial complete or major control of emesis (fewer than 3 emetic episodes in 24 hours) was achieved in 75% of patients with ondansetron compared with 42% with metoclopramide. Preliminary evidence suggests that ondansetron is as efficacious as metoclopramide in the 4 days following cisplatin chemotherapy.

In all patients included in one study, ondansetron 8mg orally three times daily provided complete or major protection against vomiting induced by single high dose upper abdominal radiotherapy, and was more effective than metoclopramide 10mg orally three times daily.

Tolerability

Overall, ondansetron is well tolerated by patients receiving radiotherapy or chemotherapy. The most frequently reported adverse event associated with ondansetron is headache, which responds to standard analgesics. However, it is noteworthy that in healthy subjects headache occurred as frequently in placebo recipients as in those receiving ondansetron. Mild constipation or diarrhoea occurs in a small minority of patients. Importantly, extrapyramidal effects such as those produced by metoclopramide would not be expected from the pharmacodynamic profile of ondansetron and have not been reported in clinical trials or in studies with healthy volunteers.

Dosage and Administration

When used to prevent nausea and vomiting induced by highly emetogenic chemotherapeutic regimens a loading dose of ondansetron 8mg infused 30 minutes before cancer therapy, with 2 additional 8mg doses administered at least 4 hours apart, or infusion of 1 mg/h for 24 hours, is recommended. For less emetogenic chemotherapeutic regimens, and for radiotherapy, ondansetron administered orally should be started as a loading dose (8mg) 1 to 2 hours prior to chemotherapy or radiotherapy and continued with 2 additional 8mg doses at 8-hour intervals. All regimens should be followed by 8mg orally for up to 5 days.

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References

  • Alphin RS, Proakis AG, Leonard CA, Smith WL, Danenburg WN, et al. Antagonism of cisplatin-induced emesis by metoclopramide and dazopride through enhancement of gastric motility. Digestive Diseases and Sciences 31: 524–529, 1986

    Article  PubMed  CAS  Google Scholar 

  • Andrews PLR, Davidson HIM. Activation of vagal afferent terminals by 5-hydroxytryptamine is mediated by the 5-HT3 receptor in the anaesthetized ferret. Proceedings of the Physiological Society, 3–4 November 1989. Journal of Physiology 422: 92P, 1990

    Google Scholar 

  • Andrews PLR, Hawthorn J. The neurophysiology of vomiting. Ballière’s Clinical Gastroenterology 2(1): 141–168, 1988

    Article  CAS  Google Scholar 

  • Andrews PLR, Rapeport WG, Sanger GJ. Neuropharmacology of emesis induced by anti-cancer therapy. Trends in Pharmacological Sciences 9: 334–341, 1988

    Article  PubMed  CAS  Google Scholar 

  • Barnes NM. Personal communication, 1990b

  • Barnes JM, Barnes NM, Costall B, Deakin JFW, Ironside JW, et al. Identification and distribution of 5-HT3 recognition sites within the human brainstem. Neuroscience Letters 111: 80–86, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Barnes JM, Barnes NM, Costall B, Ironside JW, Naylor RJ. Identification and characterisation of 5-hydroxytryptamine3 recognition sites in human brain tissue. Journal of Neurochemistry 53: 1787–1793, 1989

    Article  PubMed  CAS  Google Scholar 

  • Barnes NM, Costall B, Naylor RJ. [3 H]Zacopride: ligand for the identification of 5-HT3 recognition sites. Journal of Pharmacy and Pharmacology 40: 548–551, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Barnes NM, Costall B, Naylor RJ, Tattersall FD. Identification of 5-HT3 recognition sites in the ferret area postrema. Journal of Pharmacy and Pharmacology 40: 586–588, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Blackwell CP, Harding SM. The clinical pharmacology of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 21–24, 1989

    Google Scholar 

  • Bonneterre J, Chevallier B, Metz R, Fargeot P, Pujade-Lauraine E, et al. A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. Journal of Clinical Oncology 8: 1063–1069, 1990

    PubMed  CAS  Google Scholar 

  • Borison HL, McCarthy LE. Neuropharmacology of chemotherapy-induced emesis. Drugs 25 (Suppl. 1): 8–17, 1983

    Article  PubMed  CAS  Google Scholar 

  • Borison HL, McCarthy LE, Johnson JR. High dorsal column cordotomy plus subdiaphragmatic vagotomy prevents acute ionizing radiation sickness in cats. Experimental Neurology 98: 645–658, 1987

    Article  PubMed  CAS  Google Scholar 

  • Borison HL, Wang SC. Physiology and pharmacology of vomiting. Pharmacological Reviews 5: 193–230, 1953

    PubMed  CAS  Google Scholar 

  • Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, et al. Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Commentary. Neuropharmacology 25(6): 563–576, 1986

    Article  PubMed  CAS  Google Scholar 

  • Butler A, Hill JM, Ireland SJ, Jordan CC, Tyers MB. Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors. British Journal of Pharmacology 94: 397–412, 1988

    Article  PubMed  CAS  Google Scholar 

  • Campora E, Fosser V, Cetto G, Marangolo M, Oliva C. Ondansetron (GR38032F) in the control of acute and delayed emesis due to cancer chemotherapy regimens containing cyclophosphamide. Perugia International Cancer Conference III. Supportive Therapy: Challenges for the ’90s, p. 115, Perugia, June 14–16, 1990

  • Carden PA, Mitchell SL, Waters KD, Tiedemann K, Ekert H. Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia. Journal of Clinical Oncology 8(9): 1531–1535, 1990

    PubMed  CAS  Google Scholar 

  • Colino A, Halliwell JV. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 328: 73–77, 1987

    Article  PubMed  CAS  Google Scholar 

  • Colthup PV, Palmer JL. The determination in plasma and pharmacokinetics of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 71–74, 1989

    Google Scholar 

  • Costall B, Domeney AM, Naylor RJ, Tattersall FD. 5-Hydroxytryptamine H-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacology 25(8): 959–961, 1986

    Article  PubMed  CAS  Google Scholar 

  • Costall B, Gunning SJ, Naylor RJ, Tyers MB. The effect of GR38032F, novel 5-HT3-receptor antagonist on gastric emptying in the guinea-pig. British Journal of Pharmacology 91: 263–264, 1987

    Article  PubMed  CAS  Google Scholar 

  • Cubeddu LX, Hoffmann IS, Fuenmayor NT, Finn AL. Efficacy of ondansetron (GR 38032F) and the role of serotonin in cisplatin-induced nausea and vomiting. New England Journal of Medicine 322: 810–816, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Cubeddu LX, Hoffman IS, Fuenmayor NT, Finn AL. Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens. Journal of Clinical Oncology 8: 1721–1727, 1990b

    PubMed  CAS  Google Scholar 

  • Cunningham D, Hawthorn J, Pople A, Gazet J-C, Ford HT, et al. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet 2: 1461–1463, 1987

    Article  Google Scholar 

  • Cunningham D, Turner A, Hawthorn J, Rosin RD. Ondansetron with and without dexamethasone to treat chemotherapy-induced emesis. Letter. Lancet 2: 1323, 1989

    Article  Google Scholar 

  • Davies MF, Deisz RA, Prince DA, Peroutka SJ. Two distinct effects of 5-hydroxytryptamine on cortical neurons. Brain Research 423: 347–352, 1987

    Article  PubMed  CAS  Google Scholar 

  • de Mulder PHM, Seynaeve C, Vermorken JB, van Liessum PA, Mols-Jevdevic G, et al. Ondansetron compared with high dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. Annals of Internal Medicine 113: 834–840, 1990

    PubMed  Google Scholar 

  • du Bois A, Meerpohl HG, Wilhelm C, Quaas L, Barnickel I, et al. Therapierefraktäre Emesis unter Cisplatin. Onkologie 13: 364–368, 1990

    Article  PubMed  Google Scholar 

  • Einhorn LH, Nagy C, Werner K, Finn AL. Ondansetron: a new antiemetic for patients receiving cisplatin chemotherapy. Journal of Clinical Oncology 8(4): 731–735, 1990

    PubMed  CAS  Google Scholar 

  • Fozard JR. 5-HT3 receptors and cytotoxic drug-induced vomiting. Trends in Pharmaceutical Sciences 8: 44–45, 1978

    Article  Google Scholar 

  • Gaddum JH, Picarelli ZP. Two kinds of tryptamine receptor. British Journal of Pharmacology 12: 323–328, 1957

    CAS  Google Scholar 

  • Gandara DR, Harvey WH, Monaghan GG, Brysen JC, Finn AL. Prevention of delayed emesis following high dose cisplatin: a randomised comparative trial of ondansetron (GR 38032F) versus placebo. Perugia International Cancer Conference HI. Supportive Therapy: Challenges for the ’90s, p. 125, Perugia, June 14–16, 1990

  • Gidda JS, Evans DC, Prime P, Schenck K, Cohon ML. Role of 5HT-3 receptor antagonists in gastrointestinal motility. Gastroenterology 95: 867, 1988

    Google Scholar 

  • Gore S, Gilmore IT, Haigh CG, Brownless SM, Stockdale H, et al. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Alimentary Pharmacology and Therapeutics 4: 139–144, 1990

    Article  PubMed  CAS  Google Scholar 

  • Gralla RJ, Itri LM, Pisko SE, Squillante AE, Kelsen DP, et al. Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting. New England Journal of Medicine 305: 905–909, 1981

    Article  PubMed  CAS  Google Scholar 

  • Grunberg SM, Groshen S, Robinson DC, Stevenson LL, Sanderson PE. Correlation of anti-emetic efficacy and plasma levels of ondansetro. European Journal of Cancer 26: 879–882, 1990

    Article  PubMed  CAS  Google Scholar 

  • Grunberg SM, Stevenson LL, Russell CA, McDermed JE. Dose ranging phase I study of the serotonin antagonist GR38032F for prevention of cisplatin-induced nausea and vomiting. Journal of Clinical Oncology 7(8): 1137–1141, 1989

    PubMed  CAS  Google Scholar 

  • Hamik A, Peroutka SJ. Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer Chemotherapy and Pharmacology 24: 307–310, 1989

    Article  PubMed  CAS  Google Scholar 

  • Harrington RA, Hamilton CW, Brogden RN, Linkewich JA, Romankiewicz JA, et al. Metoclopramide: an updated review of its pharmacological properties and clinical use. Drugs 25: 451–494, 1983

    Article  PubMed  CAS  Google Scholar 

  • Hawthorn J, Cunningham D. Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret. British Journal of Cancer 61: 56–60, 1990

    Article  PubMed  CAS  Google Scholar 

  • Hawthorn J, Ostler KJ, Andrews PLR. The role of the abdominal visceral innervation and 5-HT-M receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cisplatin in the ferret. Quarterly Journal of Physiology 73: 7, 1988

    CAS  Google Scholar 

  • Hesketh PJ, Murphy WK, Lester EP, Gandara DR, Khojasteh A, et al. GR 38Ö32F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis. Journal of Clinical Oncology 7: 700–705, 1989

    PubMed  CAS  Google Scholar 

  • Hesketh PJ, Twadell T, Finn AL. A possible role for cisplatin in the transient hepatic enzyme elevations noted after ondansetron administration. Twenty Sixth Annual Meeting, May 20–22, 1990, Washington, USA. Abstract 1250. Proceedings of the American Society of Clinical Oncology, Vol. 9, March, 1990

  • Higgins GA, Kilpatrick GJ, Bunce KT, Jones BJ, Tyers MB. 5HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret. British Journal of Pharmacology 97: 247–255, 1989

    Article  PubMed  CAS  Google Scholar 

  • Indo T, Ando K. Metoclopramide-induced parkinsonism. Archives of Neurology 39: 494–496, 1982

    Article  PubMed  CAS  Google Scholar 

  • Ireland SJ, Tyers MB. Pharmacological characterization of 5-hydroxytryptamine-induced depolarization of the rat isolated vagus nerve. British Journal of Pharmacology 90: 229–238, 1987

    Article  PubMed  CAS  Google Scholar 

  • Joss R, Buser K, Piquet D, Aapro M, Cavalli F, et al. A randomised, double-blind comparison of oral ondansetron and placebo in the prophylaxis of CMF-induced nausea and vomiting. Perugia International Cancer Conference III. Supportive Therapy: Challenges for the ’90s, p. 122, Perugia, June 14–16, 1990

  • Kaasa S, Kvaløy S, Dicato MA, Ries F, Huys JV, et al. A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. European Journal of Cancer 26: 311–314, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kennard D, Butcher M, Palmer J, Beranek P, Brown GW. The anti-emetic efficacy, pharmacokinetics and safety of ondansetron in the elderly receiving cancer chemotherapy or radiotherapy. 15th International Cancer Congress (ICC), Hamburg, August 16–22, 1990. B4.252.09. Journal of Cancer Research and Clinical Oncology 116 (Suppl.): 561, 1990

    Google Scholar 

  • Khojasteh A, Sartiano G, Tapazoglou E, Lester E, Gandara D, et al. Ondansetron for the prevention of emesis induced by highdose cisplatin. A multicenter dose-response study. Cancer 66: 1101–1105, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick GJ, Jones BJ, Tyers MB. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature 330: 746–748, 1987

    Article  PubMed  CAS  Google Scholar 

  • Kilpatrick GJ, Jones BJ, Tyers MB. Binding of the 5-HT3 ligand, [3 H]GR65630, to rat area postrema, vagus nerve and the brains of several species. European Journal of Pharmacology 159: 157–164, 1989

    Article  PubMed  CAS  Google Scholar 

  • King FD, Sanger GJ. 5-HT3 receptor antagonists. Drugs of the Future 14: 875–889, 1989

    Google Scholar 

  • Kris MG, Gralla RJ, Clark RA, Tyson LB. Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. Journal of Clinical Oncology 6: 659–662, 1988

    PubMed  CAS  Google Scholar 

  • Kris MG, Gralla RJ, Clark RA, Tyson LB. Phase II trials of the serotonin antagonist GR38032F for the control of vomiting caused by cisplatin. Journal of the National Cancer Institute 81: 42–46, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kris MG, Gralla RJ, Tyson LB, Clark RA, Kelsen DP. Improved control of cisplatin-induced emesis with high-dose metoclopramide and combinations of metoclopramide, dexamethasone and diphenhydramine: results of consecutive trials in 255 patients. Cancer 55: 527–534, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kris MG, Tyson LB, Gralla RJ, et al. Extrapyramidal reactions with high-dose metoclopramide. New England Journal of Medicine 309: 433–434, 1983

    PubMed  CAS  Google Scholar 

  • Kumaya Y, Ohhashi K, Fujimura A. Clinical phase I trial of SN-307 (ondansetron). Rinsho Yakuri 21: 93–94, 1990

    Article  Google Scholar 

  • Lambert JJ, Peters JA, Hales TG, Dempster J. The properties of 5-HT3 receptors in clonal cell lines studied by patch-clamp techniques. British Journal of Pharmacology 97: 27–40, 1989

    Article  PubMed  CAS  Google Scholar 

  • Lazarus HM, Bryson JC, Lemon E, Pritchard JF, Blumer J. Antiemetic efficacy and pharmacokinetic analyses of the serotonin antagonist ondansetron (GR 38032F) during multiple-day chemotherapy with cisplatin prior to autologous bone marrow transplantation. Journal of the National Cancer Institute 82: 376, 1990

    Article  Google Scholar 

  • Leopold NA. Prolonged metoclopramide-induced dyskinetic reaction. Neurology 34: 238–239, 1984

    Article  PubMed  CAS  Google Scholar 

  • Leslie RA, Reynolds DJM, Andrews PLR, Grahame-Smith DG, Davis CJ, et al. Evidence for presynaptic 5-hydroxytryptamine, recognition sites on vagal afferent terminals in the brainstem of the ferret. Neuroscience 38: 667–673, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lucot JB. Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat. Pharmacology Biochemistry and Behavior 32: 207–210, 1989

    Article  CAS  Google Scholar 

  • Lucraft H, Palmer M. Randomized clinical trial of levonantrodol and chlorpromazine in the prevention of radiotherapy-induced vomiting. Clinical Radiology 33: 621–622, 1982

    Article  PubMed  CAS  Google Scholar 

  • Marty M, Droz JP, Pouillart P, Paule B, Brion N, et al. GR38032F, a 5HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting. Cancer Chemotherapy and Pharmacology 23: 389–391, 1989

    Article  PubMed  CAS  Google Scholar 

  • Marty M, Pouillart P, Scholl S, Droz JP, Azab M, et al. Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. New England Journal of Medicine 322: 816–821, 1990

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka O, Tsuchiya T, Furukawa Y. The effect of x-irradiation on 5-hydroxytryptamine (serotonin) contents in the small intestines of experimental animals. Journal of Radiation Research 3(2): 104, 1962

    Article  PubMed  CAS  Google Scholar 

  • McCarthy LE, Borison HL. Cisplatin-induced vomiting eliminated by ablation of the area postrema in cats. Cancer Treatment Reports 68(2): 401–404, 1984

    PubMed  CAS  Google Scholar 

  • Miner WD, Sanger GJ. Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. British Journal of Pharmacology 88: 497–499, 1986

    Article  PubMed  CAS  Google Scholar 

  • Miner WD, Sanger GJ, Turner DH. Evidence that 5-hydroxytryptamine3 receptors mediate cytotoxic drug and radiation-evoked emesis. British Journal of Cancer 56: 159–162, 1987

    Article  PubMed  CAS  Google Scholar 

  • Monković I. New benzamide anti-emetics. Drugs of the Future 14(1): 41–49, 1989

    Google Scholar 

  • Peroutka SJ. 5-Hydroxytryptamine receptor subtypes. Annual Review of Neuroscience 11: 45–60, 1988

    Article  PubMed  CAS  Google Scholar 

  • Pinkerton CR, Williams D, Wootton C, Meller ST, McElwain TJ. 5-HT3 antagonist ondansetron — an effective outpatient antiemetic in cancer treatment. Archives of Disease in Childhood 65: 822–825, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pratt GD, Bowery NG. The 5-HT3 receptor ligand [3 H]BRL 43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat. Neuropharmacology 28(12): 1367–1376, 1989

    Article  PubMed  CAS  Google Scholar 

  • Pratt GD, Bowery NG, Kilpatrick GJ, Leslie RA, Barnes NM, et al. Consensus meeting agrees distribution of 5-HT3 receptors in mammalian hindbrain. Trends in Pharmaceutical Sciences 11: 135–137, 1990

    Article  CAS  Google Scholar 

  • Priestman TJ. Clinical studies with ondansetron in the control of radiation-induced emesis. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 29–33, 1989

    Google Scholar 

  • Priestman TJ, Roberts JT, Lucraft H, Collis CH, Adams M, et al. Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation. Clinical Oncology 2: 71–75, 1990

    Article  PubMed  CAS  Google Scholar 

  • Pritchard JF, Bryson JC, Kernodle AE, Benedetti TL, Powell JR. Influence of age and gender on the pharmacokinetics of ondansetron. Abstract. Clinical Pharmacology and Therapeutics 47(2): 161, 1990

    Google Scholar 

  • Reiser G, Donié F, Binmöller F-J. Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 4-HT3 and 5-HT2 receptors by different mechanisms. Journal of Cell Sciences 93: 945–955, 1989

    Google Scholar 

  • Reiser G, Hamprecht B. Serotonin raises the cyclic GMP level in a neuronal cell line via 5-HT3 receptors. European Journal of Pharmacology — Molecular Pharmacology Section 172: 195–198, 1989

    Article  PubMed  CAS  Google Scholar 

  • Reynolds DJM, Leslie RA, Grahame-Smith DG, Harvey JM. Localization of 5-HT3 receptor binding sites in human dorsal vagal complex. European Journal of Pharmacology 174: 127–130, 1989

    Article  PubMed  CAS  Google Scholar 

  • Roila F, Tonato M, Cognetti F, Cotesi E, Favalli G, et al. A double-blind, multicentre, randomised, crossover study comparing the antiemetic efficacy and tolerability of ondansetron vs ondansetron plus dexamethasone in cisplatin treated cancer patients. Twenty Sixth Annual Meeting, May 20–22, 1990, Washington, USA. Abstract 1312. Proceedings of the American Society of Clinical Oncology, Vol. 9, March, 1990

  • Sanger GJ, King FD. From metoclopramide to selective gut motility stimulants and 5-HT3 receptor antagonists. Drug Design and Delivery 3: 273–295, 1988

    PubMed  CAS  Google Scholar 

  • Saynor DA, Dixon CM. The metabolism of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 75–77, 1989

    Google Scholar 

  • Schmoll H-J. The role of ondansetron in the treatment of emesis induced by non-cisplatin-containing chemotherapy regimes. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 35–39, 1989

    Article  Google Scholar 

  • Serve H, Perker M, Ertl A, Reichold M, Fink U, et al. Ondansetron (GR 38032F), ein kompetitiver 5-HT3-Rezeptor-Ant-agonist als Antiemetikum bei Zytostatika-induzierter Übelkeit und Erbrechen. Onkologie 13: 369–374, 1990

    Article  PubMed  CAS  Google Scholar 

  • Seynaeve C, van Liessum P, Verweij J, Lane-Allman E, de Mulder P. Control by GR38032F of acute and delayed nausea (N) and vomiting (V) induced by non-cisplatin chemotherapy. Abstract. Investigational New Drugs 7(4): 437, 1989

    Google Scholar 

  • Smith DB, Newlands ES, Rustin GJS, Begent RHJ, Crawford SM, et al. A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy. Cancer Chemotherapy and Pharmacology 25: 291–294, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Smith DB, Newlands ES, Spruyt OW, Begent RHJ, Rustin GJS, et al. Ondansetron (GR38032F) plus dexamethasone: effective anti-emetic prophylaxis for patients receiving cytotoxic chemotherapy. British Journal of Cancer 61: 323–324, 1990b

    Article  PubMed  CAS  Google Scholar 

  • Smith RN. Safety of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): 47–50, 1989

    Article  Google Scholar 

  • Stables R, Andrews PLR, Bailey HE, Costall B, Gunning SJ, et al. Antiemetic properties of the 5HT3-receptor antagonist, GR38032F. Cancer Treatment Reviews 14: 333–336, 1987

    Article  PubMed  CAS  Google Scholar 

  • Stott JRR, Barnes GR, Wright RJ, Ruddock CJS. The effect on motion sickness and oculomotor function of GR 380323F, a 5-HT3-receptor antagonist with anti-emetic properties. British Journal of Clinical Pharmacology 27: 147–157, 1989

    Article  PubMed  CAS  Google Scholar 

  • Talley NJ, Phillips SF, Haddad A, Miller LJ, Twomey C, et al. Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides. Digestive Diseases and Sciences 34(10): 1511–1515, 1989

    Article  PubMed  CAS  Google Scholar 

  • Talley NJ, Phillips SF, Haddad A, Miller LJ, Twomey C, et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man. Digestive Diseases and Sciences 35(4): 477–480, 1990

    Article  PubMed  CAS  Google Scholar 

  • Triozzi PL, Laszlo J. Optimum management of nausea and vomiting in cancer chemotherapy. Drugs 34: 136–149, 1987

    Article  PubMed  CAS  Google Scholar 

  • Tyers MB, Bunce KT, Humphrey PP. Pharmacological and antiemetic properties of ondansetron. European Journal of Cancer and Clinical Oncology 25 (Suppl. 1): S15–S19, 1989

    CAS  Google Scholar 

  • van Liessum PA, Seynaeve C, de Mulder PH, Kaasa S, Lane-Allman E, et al. Ondansetron in the prophylaxis of nausea and vomiting induced by cisplatin. European Journal of Cancer 26: 769–770, 1990

    Article  PubMed  Google Scholar 

  • Viner CV, Selby PJ, Zulian GB, Gore ME, Butcher ME, et al. Ondansetron — a new safe and effective antiemetic in patients receiving high-dose melphalan. Cancer Chemotherapy and Pharmacology 25: 449–453, 1990

    Article  PubMed  CAS  Google Scholar 

  • Werner K, Finn AL, Gandara DR. Maintenance of anti-emetic effectiveness with multiple courses of GR 38032F and cisplatin. Proceedings of the American Society of Clinical Oncology 8: 327, 1989

    Google Scholar 

  • Yakel JL, Trussel LO, Jackson MB. Three serotonin responses in cultured mouse hippocampal and striatal neurons. Journal of Neuroscience 8: 1273–1285, 1988

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Adis Drug Information Services, Auckland, New Zealand

    Richard J. Milne

  2. Adis International Limited, 41 Centorian Drive, Mairangi Bay, Auckland 10, New Zealand

    Rennie C. Heel

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  1. Richard J. Milne
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Various sections of the manuscript reviewed by: P.R. Andrews, Department of Pharmacology, St Georges Medical School, London, England; N.M. Barnes, University of Bradford, Bradford, England; H.L. Borison, Dartmouth Medical School, Hanover, New Hampshire, USA; J. Bonneterre, Centre Oscar Lambret, Lille, France; B. Costall, University of Bradford, Bradford, England; T. Itoh, Tottori University School of Medicine, Japan; M.G. Kris,Solid Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA; J. Mansi, The Royal Marsden Hospital, England; R.J. Naylor, University of Bradford, Bradford, England; T.J. Priestman, Queen Elizabeth Hospital, Birmingham, England; S. Saito, The University of Tokushima, Tokushima, Japan; H.J. Schmoll, Medizinische Hochschule, Hannover, Federal Republic of Germany.

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Milne, R.J., Heel, R.C. Ondansetron. Drugs 41, 574–595 (1991). https://doi.org/10.2165/00003495-199141040-00006

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