Clinical Pharmacokinetics of Metoclopramide
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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.
KeywordsClinical Pharmacology Metoclopramide Clinical Pharmacokinetic Total Body Clearance Liver Blood Flow
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