L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
717 
tribution. It may be noted that the apparent 
specific volume of distribution of salicylate in 
the goat was approximately 75% that calcu- 
lated for the pig and pony. 
The herbivorous animals conjugated salicy- 
late with glycine at a much more rapid rate 
than did the omnivorous pig or carnivorous dog. 
Rate of glucuronidation of salicylate was higher 
in the goat and dog than in the pony and pig. 
The species differences in rate of excretion of 
unchanged salicylate was related in part to uri- 
nary hydrogen ion concentration. The pH of 
goat urine averaged 8.2 and pony urine 7.6 
while pig urine was 6.4 and dog urine 5.8. This 
observation is in agreement with the relation- 
ship between urinary pH and renal clearances 
of salicylate reported by Smith and co-workers 
in human patients. 
The cat was handicapped in several ways in 
its ability to excrete salicylate. It was deficient 
in the ability to synthesize metabolites which 
are more polar than the parent compound and 
the urine was quite acid (pH 5.2) thereby de- 
creasing renal clearance of the drug. 
Data on the effects of chronic administration 
of the drug showed no changes in plasma half- 
life and the distribution of salicyl metabolites in 
urine remained constant over the six-month pe- 
riod in the control groups. The percentage of 
unchanged salicylate remained fairly constant 
in the low and therapeutic dose groups whereas 
the high dose groups excrete a larger percent- 
age of salicylate after six months of chronic 
administration. The percentages of salicylglucu- 
ronide increased as a result of chronic adminis- 
tration and this increase was at the expense of 
salicylurate synthesis in all species. This would 
suggest the possible induction of glucuronyl 
transferase. No untoward effects of the drug 
were noted except in cats. Cumulation of the 
drug produced ulceration of the GI tract with 
hemorrhage. No changes were noted in the he- 
mograms which could be attributed to the drug 
and no fetal anomolies were observed. 
Absorption, following oral, administration, 
was found to be rapid and complete in all spe- 
cies except the goat. In this species we observed 
several absorption peaks in the plasma over the 
12-hour periods studied. These probably are re- 
lated to periodic overflow of rumen contents 
into the abomasum or true stomach. These data 
are shown in Figure 2. Plasma protein-binding 
was studied in each species, including man. 
These data are tabulated in Table II. 
Phenol 
Phenol and its synthesized metabolites, 
phenyl sulfate and phenylglucuronide, were 
characterized by physical properties and sepa- 
rated by chromatography. LD 50*s were deter- 
mined and revealed effective phenol detoxication 
by conjugation with sulfate and glucuronate. A 
200- Dogs 
200- Goats 
150- 
100- 
50- 
0 l^ "*^^^^T=-* - f ■ T^'S ' T , 
2 4 6 8 10 12 
time (hrs.) 
Figure 2. — Species differences in absorption of sodium 
salicylate following the oral administration of the 
drug contained in gelatin capsules. Three dosage lev- 
els (18.5, 50 and 133 mg/kg) were studied. The data 
points represent the means from at least four ani- 
mals. 
