The pharmacokinetics of metoclopramide in man with observations in the dog

1 The pharmacokinetics of metoclopramide have been studied in eight normal male volunteers. 2 The mean plasma beta half-life was 156.7 min after i.v. administration of 10 mg metoclopramide. 3 After oral dosing of 10 mg the mean half-life was 196.6 min and after 20 mg 317.5 min (P less than 0.05). 4 Bioavailability of a 10 mg oral dose of metoclopramide varied between 32 and 97%. 5 A major urinary metabolite was metoclopramide-N-4-sulphate and the amounts of conjugates appearing in urine to 24 h correlated significantly with the bioavailability. 6 In the dog the metabolic fate of metoclopramide is different to man with conjugation being a minor metabolic pathway. The half-life in the dog does not appear to be dose dependent. 7 The wide differences in bioavailability of metoclopramide in man may contribute to the unpredictable occurrence of side effects.