Clinical pharmacokinetics in veterinary medicine

Abstract

Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or pharmacodynamic activity, or both. When administering a drug orally, the bioavailability from a dosage form can vary widely. This is particularly the case between ruminant animals (cattle, sheep and goats), horses and carnivorous species (dogs and cats). Species variations in bioavailability can be avoided by parenteral administration. Formulation of parenteral preparations and location of intramuscular injection site can, at least in horses and cattle, influence bioavailability. Comparative pharmacokinetic studies help to explain differences in absorption and disposition processes that may underlie species variations in response to fixed dosages of a drug. Certain marker substances are useful in quantifying the activity of metabolic pathways or efficiency of excretion processes. Prediction of preslaughter withdrawal times in food-producing animals represents an application of pharmacokinetics in the field of drug residues. The drug residue profile can be obtained by combining fixed dose pharmacokinetic studies with measurement of drug concentrations in selected tissues and organs of the body. This approach offers an economical advantage in that fewer animals are required for residue studies. In domestic animals, as in humans, the disposition of most drugs can be interpreted in terms of a 2- (generally) or 3-compartment open model. Species variations in pharmacokinetic behaviour of a drug are usually attributed to differences in the rate of elimination rather than distribution and metabolism of the drug, although the principal metabolic pathway may differ. With certain notable exceptions, the herbivorous species (horses and ruminant animals) metabolise lipid-soluble drugs more rapidly than carnivorous species (dogs and cats). Humans metabolise drugs slowly in comparison with animals. Half-life values reflect this; insufficient data are available to base interspecies comparison on mean residence time. Intrinsic hepatic clearance of phenazone (antipyrine) [microsomal oxidation] in humans is approximately one-seventh of that in domestic animals.(ABSTRACT TRUNCATED AT 400 WORDS)