Bolus and infusions of metoclopramide: insights on benefits and risks from pharmacokinetic modelling.

Metoclopramide is used for prevention or treatment of emesis and gastroesophageal reflux in dogs. Historically, it has been administered three to four times a day. However, reports of adverse reactions associated with intravenous boluses raise concerns. A more modern trend is to administer the total daily dose as a constant rate infusion of 1 to 2 mg/kg/day. A loading dose prior to the infusion is often omitted, which can delay the onset of action. Adequate loading doses for these constant rate infusions are not known. We have reanalysed pharmacokinetic data from dogs receiving metoclopramide and modelled its behaviour when administered as a constant rate infusion, with and without loading doses. We have quantified the delay expected if loading doses are not administered and calculated appropriate loading doses designed to reach the target concentration while omitting unnecessarily high plasma levels. If a loading dose is omitted, a delay of 3.25 hours for reaching a steady state can be expected. Loading doses of 0.05 and 0.1 mg/kg are recommended for infusions of 1 and 2 mg/kg/day, respectively, in order to reach targeted plasma levels almost immediately.