L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
731 
PENTOBARBITAL (10mg/kg,IV) 
O O CMS 
# 0 DOGS 
□ Q GOATS 
O O PONIES 
- SWINE 
Figure 18. — Disappearance of pentobarbital from the 
plasma of several species following intravenous ad- 
ministration (10 mg/kg). 
with oxidative mechanisms. For example, cats 
were quite efficient in the transformation of me- 
peridine (N-dealkylation) and phenylbutazone 
(aromatic hydroxylation) . The primary impor- 
tance of biotransformation to the problem of 
species differences was well-illustrated by the 
study of tetraethylammonium. This drug is not 
metabolized in the body and species differences 
in rate of elimination were not observed. 
Factors other than biotransformation may be 
important determinants of species differences 
in disposition of some drugs. Species differences 
in plasma protein-drug interaction were found 
to be important in the case of quinidine and 
phenylbutazone. Difference in specific apparent 
volume of distribution was an important deter- 
minant of duration of action of pentobarbital. 
In general, basic drugs had large volumes of 
distribution indicative of sequestration in the 
body and acidic drugs had much smaller vol- 
umes of distribution. 
The results of this investigation illustrate the 
futility of attempting to extrapolate informa- 
tion derived from one species of animal to an- 
other species. We would conclude on the basis of 
our experience that any drug should be evalu- 
ated in the animal species in which it is to be 
used rather than attempt to apply information 
obtained in one species to another. Thus, the ul- 
timate aim of this investigation was not at- 
tained. I don't believe that it is possible to de- 
velop an animal system which would predict the 
implications of drug therapy in man. 
REFERENCES 
1. Brodie, B. B. Clinical implications of drug metabo- 
lism. Proc. Mid- Year Meeting, Amer. Pharmaceut. 
Manufact. Assn., 122-143, 1952. 
2. Williams, R. T. Detoxication Mechanisms. 2nd 
ed. John Wiley & Sons, N. Y. 1959. 
3. Done, A. K. Developmental pharmacology. Clin. 
Pharmacol. Therap. 5:432, 1964. 
TETRAETHYLAMMONIUM 10 mg/kg 
Figure 19. — Disappearance of tetraethylammonium 
from the plasma of dogs, cats and goats following in- 
travenous administration ( 50 mg/kg) . 
