Single-dose pharmacokinetics of metoclopramide

Abstract

The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i. v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h +/- 0.80 h and a mean distribution half-time of 0.35 h +/- 0.09 h. Volumes of distribution were high (3.43 +/- 1.181 . kg-1), and clearances (0.53 +/- 0.191 . kg-1 h-1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The postabsorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h +/- 0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of "first-pass' was considerable (0.47--1.14).

The pharmacokinetics of high dose metoclopramide in patients with neoplastic disease.

“…Hepatic metabolism is the major component of metoclopramide elimination with clearance approximating to liver blood flow (Bateman et al, 1978;Ross-Lee et al, 1981). Three metabolites have been identified in man; the most predominant is the N-4 sulphate derivative and over 40% of an oral dose may be excreted in this form.…”

Linearity of metoclopramide kinetics at doses of 5‐20 mg.

“…Furthermore, many attempts to examine the bioavailability of metoclopramide (Block et al, 1979;Schuppan et al, 1979;Graffner et al, 1979;Bateman et al, 1980) used unequal intravenous and oral dosages of metoclopramide, which, in view of the uncertainty regarding the dose-linearity of kinetics seemed inappropriate. Finally, several groups had tried to approximate the relative bioavailability of metoclopramide using an oral tablet as the oral reference dosage form (Schuppan et al, 1979;Graffner et al, 1979;Bateman et al, 1980;Ross-Lee et al, 1981), which may have confused the interpretation of the extent of first-pass metabolism.…”

The Effect of Metoclopramide in Capsule Enteroscopy

“…Effects of metoclopramide in gastrointestinal motility may reach the sigmoid colon and high-amplitude peristaltic waves are observed over the total length of duodenum [27]. It has a rapid and good oral absorption, with mean bioavailability of 77%, a peak plasma concentration at 56 min and a half-life of 5 h [28]. It has a high safety profile even at an oral dose of 20 mg [29] and is readily available and inexpensive.…”