Improved benefit/risk ratio of higher-dose metoclopramide therapy during cisplatin-induced emesis

Metoclopramide (Paspertin) was infused intravenously in the high doses of 1.75, 3.5, 7.0, and 14 mg/kg body wt. per treatment cycle as antiemetic therapy for cisplatin-induced emesis (363 cycles, 25-120 mg/m2). The antiemetic potency of metoclopramide increased in a log linear manner, giving from 40% to 95% protection against emesis. Gastrointestinal motility showed a similar increase, i.e. diarrhoea. In contrast, the extrapyramidal reactions, namely akathisia, rigidity and acute dystonia, did not show a dose-dependent increase in frequency and remained constant over the dose range of 3.5-14 mg/kg per cycle. The results suggest increasing benefit of metoclopramide treatment with increasing doses of the drug.