Abstract
A few studies indicate a dose–response effect of the antiemetic metopimazine. The aim of this study was therefore to investigate the tolerability of increasing doses of metopimazine given orally every 4 h for eleven doses. The dose levels 20 mg, 30 mg, 40 mg, 50 mg and 60 mg were studied in 36 patients completing 46 cycles of chemotherapy. Serum concentrations of metopimazine and the acid metabolite AMPZ were measured by HPLC in 13 patients (15 cycles). The dose-limiting toxicity was moderate to severe dizziness caused by orthostatic hypotension as seen in 0, 0, 17%, 42% and 50% of patients at the respective dose levels. Other side effects were few and mild, and only a single possible extrapyramidal adverse event was observed in a patient at the 60-mg dose. High serum concentrations were not predictive for toxicity, as found on comparison of patients with and without symptoms, but in individual patients symptoms were seen at the time of Cmax. We found that metopimazine was safe with a dosage of 30 mg × 6. This dose is four times higher than that previously recommended for antiemetic use.
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References
Aapro MS (1991) 5-HT3 receptor antagonists. An overview of their present status and future potential in cancer chemotherapy-induced emesis. Drugs 42:551–568
Angelo HR, Herrstedt J, Jørgensen M (1989) High-perfomance liquid chromatographic method with fluorescence detection for the simultaneous determination of metopimazine and its acid metabolite in serum. J Chromatogr 496:472–477
Carr BI, Blayney DW, Goldberg DA, Braly P, Metter GE, Doroshow JH (1987) High doses of prochlorperazine for cisplatin-induced emesis: a prospective, random, dose-response study. Cancer 60:2165–2169
Clavel M, Bolot JE, Philippe-Bert J, et al (1978) Double-blind comparative trial with metopimazine (50 mg and 10 mg i.v.) as a preventive treatment for nausea and vomiting attending anticancer drug therapy. Lyon Med 239:307–309
Debray H, Giuhard J, Peyramond D, Tron P (1990) Treatment of vomiting in infants and children induced by acute infectious pathology. A comparative study of alizapride versus metopimazine. Ann Pediatrie 37:683–687
Gralla RJ, Itri L, Pisko S, et al (1981) Antiemetic efficacy of high dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced vomiting. N Engl J Med 305:905–909
Grunberg SM, Gala KV, Lampenfeld M, et al (1984) Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study. J Clin Oncol 2:782–787
Herrstedt J, Jørgensen M, Angelo HR (1990) The effect of food on serum concentrations of metopimazine. Br J Clin Pharmacol 30:237–243
Herrstedt J, Hyttel J, Pedersen J (1993) Interaction of the antiemetic metopimazine and anticancer agents with brain dopamine D2, 5-hydroxytryptamine3, histamine H1, muscarine cholinergic andα 1-adrenergic receptors. Cancer Chemother Pharmacol 33:53–56
Herrstedt J, Sigsgaard T, Boesgaard M, et al (1993) Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy. N Engl J Med 328:1076–1080
Homesley HD, Gainey JM, Jobson VN, et al (1982) Double-blind placebo-controlled study of metoclopramide in cisplatin-induced emesis. N Engl J Med 307:250–251
Israel L, Rodary C (1978) Treatment of nausea and vomiting related to anticancerous multiple combination chemotherapy: results of two controlled studies. J Int Med Res 6:236–240
Kris MG, Tyson LB, Clark RA, Gralla RJ (1992) Oral ondansetron for the control of delayed emesis after cisplatin. Report of a phase II study and review of completed trials to manage delayed emesis. Cancer 70:1012–1016
Miner WD, Sanger GJ (1986) Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol 88:497–499
Moertel CG, Reitemeier RJ (1969) Controlled clinical studies of orally administered antiemetic drugs. Gastroenterology 57:262–268
Moertel CG, Reitemeier RJ (1973) Controlled studies of metopimazine for the treatment of nausea and vomiting. J Clin Pharmacol 57:283–287
Olver IN, Webster LK, Bishop JF, et al (1989) A dose finding study of prochlorperazine as an antiemetic for cancer chemotherapy. Eur J Cancer Clin Oncol 25:1457–1461
Olver IN, Wolf M, Laidlaw C, et al (1992) A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy. Eur J Cancer 28A:1798–1802
Seigneuric C, Plantavid M, Sorbette F, et al (1983) Extrapyramidal syndrome. Possible role of metopimazine (letter). Presse Med 12:962–963
Siegel S, Castellan NJ Jr (1988) Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York
Tonkin A, Wing L (1992) Aging and susceptibility to drug-induced orthostatic hypotension. Clin Pharmacol Ther 52:277–285
Vallejo C, Rabinovich M, Leone B, et al (1988) Toxicity and dose-response of intravenous (i.v.) metopimazine (MTZ) as preventive of highdose cisplatin (CDDP)-induced emesis. Proc Am Soc Clin Oncol 7:286
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Herrstedt, J., Sigsgaard, T., Angelo, H.R. et al. Dose-finding study of oral metopimazine. Support Care Cancer 5, 38–43 (1997). https://doi.org/10.1007/BF01681960
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DOI: https://doi.org/10.1007/BF01681960