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Clinical Pharmacokinetics of Metoclopramide

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Summary

Metoclopramide is rapidly and well absorbed from the gastrointestinal tract, and in man undergoes variable first-pass metabolism (oral bioavailability 32 to 100%). In man, N-4 sulphate conjugation is an important pathway of metabolism and after oral administration the ratio of free to conjugated metoclopramide in urine correlates with the plasma AUC.

The elimination half-life of metoclopramide is dose-dependent after both intravenous and oral administration of single doses between 5 and 20mg. Metabolic profiles in animal species studied are very different from man. The clearance of metoclopramide is reduced in patients with renal failure to approximately 50% of normals and the terminal half-life is prolonged; this is despite the fact that renal clearance of free drug accounts for only 20% of the administered dose in normals.

Preliminary studies after ‘high dose’ metoclopramide demonstrate accumulation to high plasma concentrations with linear kinetics, suggesting that current high dose regimens are unnecessarily cumbersome.

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Authors and Affiliations

  1. Wolfson Unit of Clinical Pharmacology, The University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, England

    D. Nicholas Bateman

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Bateman, D.N. Clinical Pharmacokinetics of Metoclopramide. Clin Pharmacokinet 8, 523–529 (1983). https://doi.org/10.2165/00003088-198308060-00003

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