Pharmacokinetics and efficacy of high-dose metoclopramide given by continuous infusion for the control of cytotoxic drug-induced vomiting.

To avoid the accumulation of metoclopramide that occurs with repeated i.v. bolus doses, a new regimen for the administration of high-dose metoclopramide consisting of a loading dose followed by a continuous infusion was investigated to determine the pharmacokinetics and antiemetic efficacy of the drug when given in this manner. Nine patients with non-Hodgkin's lymphoma entered the study, of whom six completed the study, receiving each of three dosage schedules of metoclopramide during three consecutive courses of chemotherapy. In these six patients plasma metoclopramide half-life was 5.9 +/- 0.4 h (mean +/- s.e. mean) and plasma clearance was 25.4 +/- 4.8 l/h (mean +/- s.e. mean). Neither half-life nor clearance were dose-related. Steady-state was achieved during 9/18 infusions. Nausea and vomiting were completely controlled in 13/24 treatment courses (57%) and adverse effects were minimal. We conclude that steady-state plasma concentrations of metoclopramide can be achieved using a weight-related infusion regimen, though the optimum plasma concentration remains to be determined.