Jones RD, Mizinga KM, Thompson FN, Stuedemann JA & Bowen JM
Bioavailability and pharmacokinetics of metoclopramide in cattle.

J Vet Pharmacol Ther, 17(2): 141-147, 1994
ISSN: 0140-7783 Journal of Veterinary Pharmacology and Therapeutics (PubMed)

Abstract
The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (+/- SD) oral and abomasal bioavailabilities were 51.3 +/- 30.7% and 76.2 +/- 15.5%, respectively. The mean value for clearance (Cl) was 20.1 +/- 5.9 ml/min and the volume of distribution (V(d)) was 0.51 +/- 0.19 l/kg. Additional pharmacokinetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t( [half] alpha) harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t( [half] beta) harmonic mean of 53.1 min and a range of 31.1-134.1 min, a Cl of 42.2 +/- 8.7 ml/min, and a V(d) of 2.1 +/- 0.8 l/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration (MCP(ss)) of 8.8 +/- 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 +/- 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRL(ss)) did not rise significantly above 23.3 +/- 6.9 ng/ml, even when MCP(ss) reached a concentration of 518.5 +/- 151.2 ng/ml. The short half-life, moderate V(d), low minimum pharmacologically effective concentration, and rapid Cl found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.