730 
PHARMACOLOGY 
90l 
80 
70 
60 
" 50 
^ 40 
t 30 
a: 20 
10 
-X GOAT 
— DOG 
PALPEBRAL REFLEX RETURNED 
RIGHTING REFLEX RETURNED 
AWAKE 
100 200 300 400 500 600 700 800 900 1000 
TIHE (Ml MUTES) 
Figure 17. — Concentrations of pentobarbital in plasma of dogs and goats following intravenous administration 
(25 mg/kg). Arrows indicate the drug concentrations and times at which reflexes returned. 
SUMMARY 
The major objectives of this investigation 
were the definition of species differences in 
pharmacokinetics of various drugs, the identifi- 
cation of urinary metabolites and effects of 
chronic administration on these parameters. 
These objectives were attained. The scope of the 
problem of species differences w^as well deline- 
ated by the results reported here. With several 
drugs the entire spectrum of possible disap- 
pearance rates was represented by the species 
studied. For example, salicylate and phenol 
were very rapidly eliminated from the plasma 
of goats and ponies but were slowly eliminated 
from cats. On the other hand, drugs which were 
metabolized by oxidative mechanisms were 
more rapidly eliminated by the cat. There were 
few general principles to be derived during the 
course' of these studies. Sex differences did not 
occur with most drugs and are not considered to 
be an important phenomenon. 
It is apparent from these studies, that in 
most cases, the crucial factor in determining 
species differences in persistence of drugs is 
that of rate of biotransformation. Species dif- 
ferences in elimination of drugs which are 
transformed primarily by conjugation mecha- 
nisms are more nearly predictable than are 
compounds which are metabolized by oxidation 
or reduction. Herbivorous animals had the 
greatest capacity for conjugation of xenobiot- 
ics, carnivores had the least and omnivores 
were intermediate. It appears in some cases, 
that animals which were handicapped in their 
ability to conjugate drugs were well-endowed 
