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 (Vd) 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 1/2 alpha harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t 1/2 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 Vd 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 (MCPss) 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 (PRLss) did not rise significantly above 23.3 +/- 6.9 ng/ml, even when MCPss reached a concentration of 518.5 +/- 151.2 ng/ml. The short half-life, moderate Vd, 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.
Jones
R D
RD
Department of Veterinary Physiology and Pharmacology, University of Georgia, Athens 30602.
Mizinga
K M
KM
Thompson
F N
FN
Stuedemann
J A
JA
Bowen
J M
JM
D000018:Abomasum / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002417:Cattle / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D007262:Infusions, Intravenous / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011388:Prolactin / Q000097:blood; D014018:Tissue Distribution
D011388:Prolactin; D008787:Metoclopramide