BIOAVAILABILITY AND PHARMACOKINETICS OF METOCLOPRAMIDE IN CATTLE

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 determi ned following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t1/ 2alpha harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t1/2b eta harmonic mean of 53.1 min and a range of 31.1-134.1 min, a Cl of 4 2.2 +/- 8.7 ml/min, and a V(d) of 2.1 +/- 0.8 1/kg. To better define t he relationship between metoclopramide concentration and release of pr olactin, 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 mea n value of 12.1 +/- 3.1 ng/ml in six yearling steers. Steady state ser um 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 pha rmacologically effective concentration, and rapid Cl found for metoclo pramide in cattle in this study, suggest that a continuous release dev ice could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.