High-dose metoclopramide by infusion: a double-blind study of plasma concentration-effect relationships in patients receiving cancer chemotherapy

Abstract

We have carried out a randomized, double-blind trial to investigate the relationship between the dose and plasma concentration of metoclopramide and its anti-emetic efficacy and adverse effects in patients receiving cancer chemotherapy. Seventeen patients received four different infusion regimens of high-dose metoclopramide in random order with four consecutive courses of chemotherapy, to achieve an approximately eight-fold range in plasma metoclopramide concentrations. In patients receiving cisplatin the incidence of vomiting decreased with increasing metoclopramide dose, but the overall efficacy was poor. There was no relationship between anti-emetic efficacy and either dose or plasma concentration of metoclopramide in patients receiving cyclophosphamide and doxorubicin. The adverse effects of high-dose metoclopramide included diarrhoea, which increased in incidence with increasing metoclopramide dose, and sedation and extrapyramidal reactions, which were not related to dose or plasma concentration. Although anti-emetic efficacy increases with increasing metoclopramide dose in patients receiving cisplatin, high-dose metoclopramide alone does not adequately control cisplatin-induced nausea and vomiting.