COMPARATIVE PHARMACOKINETICS IN 
DOMESTICATED ANIMALS 
L. E. Davis, C. H. Davis and J. D. Baggot' 
We studied a series of drugs, selected on the basis of 
their physico-chemical properties, in ponies, goats, 
swine, dogs and cats. The drugs included five acidic 
drugs (salicylate, pentobarbital, phenylbutazone, oxy- 
phenylbutazone and phenol) and five basic drugs (penta- 
zocine, chloramphenicol, quinidine, amphetamine and 
tetraethylammonium) . Parameters measured or com- 
puted included: elimination rate constants, drug con- 
centrations in plasma, volumes of distribution and ex- 
tent of drug-plasma protein binding. Drug absorption 
from depot sites following oral or intramuscular admin- 
istration was investigated for some of the drugs. Some 
patterns in species differences were evident in our inves- 
tigations. Drugs which were eliminated as conjugates 
with glucuronic acid, sulfate or glycine were eliminated 
from the body rapidly in herbivorous animals and 
slowly in carnivorous animals; omnivorous animals 
were intermediate. The cat was particularly handi- 
capped in its ability to eliminate such compounds. Pat- 
terns were not predictable for drugs which were trans- 
formed by oxidative mechanisms. Specific volume of 
distribution for individual drugs was largest in rumi- 
nant animals and was much larger for basic drugs than 
for acidic drugs. In general, rates of elimination were 
not related to extent of drug-protein interaction, al- 
though species differences were observed in plasma pro- 
tein binding of various drugs. From our experiments, 
we found marked species differences in the time course 
of drug concentrations in the plasma of representative 
large domesticated animals. This work illustrates the er- 
rors which may be encountered when one attempts to 
extrapolate information concerning drugs from one 
species to another. 
INTRODUCTION 
Relatively little is known regarding the time 
course of drug concentrations in the plasma of 
species other than man and the common labora- 
tory animals. Such information is a necessary 
prerequisite for the determination of dosage 
regimens and interpreting experimental data. 
Brodie^ indicated the need for information 
relative to species differences in the rate of me- 
• Division of Comparative Pharmacology, Department of Veteri- 
nary Physiology and Pharmacology, College of Veterinary Medicine, 
The Ohio State University, Columbus, Ohio. 
tabolism of drugs. On the basis of the impor- 
tance of this knov^ledge to the preclinical test- 
ing of new drugs, it has been suggested that a 
search should be made for animal species which 
metabolize given classes of compounds at the 
same rate as does man.^'^ Knowledge of the 
disposition and fate of drugs in large farm ani- 
mals is extremely limited and systematic inves- 
tigations of pharmacokinetics in these species 
have not been conducted. Accordingly we have 
studied the time-course of drug concentrations 
for several drugs in ponies, goats, swine, dogs 
and cats. 
MATERIAL AND METHODS 
Animals 
The animals employed in these studies were 
sexually mature Shetland cross ponies, Hamp- 
shire and Yorkshire swine. Angora goats, mon- 
grel dogs and American short haired cats of 
both sexes. All subjects were healthy at the 
time of the experiments. 
During the experiments animals were con- 
fined to metabolism cages or crates. The partic- 
ular drug of interest was administered and 
blood samples were collected at appropriate in- 
tervals. Urine samples were collected for 24 
hours. Retention catheters were passed into the 
urinary bladders of mares, does and sows. 
Voided urine was collected from all other ani- 
mals. All samples were analyzed immediately or 
frozen pending analysis. 
Analytical Procedures 
The concentrations of the various drugs were 
determined by established procedures as fol- 
lows: salicylate,'* pentobarbital,^ phenylbuta- 
zone,^ phenol,^ pentazocine,^ chloramphenicol,® 
quinidine,^" and amphetamine." Tetraethylam- 
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