Dose-finding study of oral metopimazine

• Published in: Supportive care in cancer Vol. 5; no. 1; pp. 38 - 43
• Main Authors: HERRSTEDT, J, SIGSGAARD, T, ANGELO, H. R, KAMPMANN, J. P, HANSEN, M
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 1997; Berlin Springer Nature B.V
• Subjects: Administration, Oral; Adult; Age Factors; Aged; Antiemetics - administration & dosage; Antiemetics - adverse effects; Antiemetics - blood; Antiemetics - metabolism; Antiemetics - pharmacokinetics; Antineoplastic Agents - adverse effects; Basal Ganglia Diseases - chemically induced; Biological and medical sciences; Blood Pressure - drug effects; Dizziness - chemically induced; Dose-Response Relationship, Drug; Drug therapy; Drug toxicity and drugs side effects treatment; Female; Forecasting; Headache - chemically induced; Humans; Hypotension, Orthostatic - chemically induced; Isonipecotic Acids - administration & dosage; Isonipecotic Acids - adverse effects; Isonipecotic Acids - blood; Isonipecotic Acids - metabolism; Isonipecotic Acids - pharmacokinetics; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Sleep Stages - drug effects; Toxicity: digestive system; Xerostomia - chemically induced; Antineoplastic agent; Human; Dopamine; Toxicity; Oral administration; Phenothiazine derivatives; Malignant tumor; Dose activity relation; Chemotherapy; Treatment; Vomiting; Metopimazine; Digestive diseases; Complication; Antagonist; Antiemetic
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/BF01681960

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 x 6. This dose is four times higher than that previously recommended for antiemetic use.