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Dose-finding study of oral metopimazine
J Herrstedt1, T Sigsgaard, H R Angelo
1Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
Summary
Metopimazine, an antiemetic, was found safe at higher doses (30 mg x 6) in chemotherapy patients. This dose, four times the previous recommendation, showed manageable side effects, primarily dizziness.
Area of Science:
- Pharmacology
- Clinical Therapeutics
Background:
- Limited data exists on the dose-response relationship of the antiemetic metopimazine.
- Previous recommendations for metopimazine dosage may not fully leverage its antiemetic potential.
Purpose of the Study:
- To investigate the tolerability of escalating oral doses of metopimazine.
- To determine the safety profile of metopimazine at higher dosages in patients undergoing chemotherapy.
Main Methods:
- A dose-escalation study involving 36 patients undergoing chemotherapy.
- Oral metopimazine administered every 4 hours for eleven doses, with dose levels ranging from 20 mg to 60 mg.
- Serum concentrations of metopimazine and its metabolite AMPZ measured via HPLC in a subset of patients.
Main Results:
- The dose-limiting toxicity was moderate to severe dizziness associated with orthostatic hypotension, increasing with dose (0% at 20-30 mg, 50% at 60 mg).
- Few other side effects were observed, with only one possible extrapyramidal event at the highest dose.
- High serum concentrations did not consistently predict toxicity, though symptoms correlated with Cmax in individuals.
Conclusions:
- Metopimazine demonstrated safety and tolerability at a dosage of 30 mg every 4 hours (30 mg x 6).
- This effective antiemetic dose is four times higher than previously recommended, suggesting potential for improved symptom control in chemotherapy patients.
- Further research into optimized metopimazine dosing for antiemesis is warranted.