L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
719 
cats. The extent of plasma protein binding of 
phenol was about 60% in all species. The total 
endogenous phenols excreted in the urine of 
normal animals in 24 hours was less than 0.5 
mg/kg in dogs, slightly more than 2 mg/kg in 
cats, slightly more than 3 mg/kg in swine and 
7.5 mg/kg in goats. Dog urine contained equal 
portions of free phenol, phenylsulfate and 
phenylglucuronide. Cats excreted phenol pri- 
marily as phenylsulfate. Pigs excreted the 
phenol primarily as glucuronide and goat urine 
contained largely phenylsulfate with some free 
phenol. Injected phenol was excreted in the 
spine as free phenol, phenylsulfate and phenyl- 
glucuronide. The proportions of each varied 
with the species and followed the pattern of 
excretion of the endogenous phenols. 
The lack of phenolic oxidation products was 
related to the rapid conjugation afforded by the 
intravenous route of administration. Phenylsul- 
fate excretion reached a maximum and re- 
mained constant at dosages above 50 mg/kg 
(saturation) . Phenylglucuronide excretion rates 
progressively increased with increases in dose. 
The excretion rate of phenylglucuronide in 
cats was the lowest of all of the animals stud- 
ied and increased the least with each dose in- 
crease. Injected phenylsulfate and phenylglucu- 
ronide were rapidly cleared from the plasma 
and were completly accounted for in the 24- 
hour urine sample. Similar clinical effects were 
observed in all species at similar plasma levels. 
However, cats were more severely affected by 
given dosages of phenol than were dogs, swine 
and goats. This was explained by differences in 
disposition and fate of phenol within the body. 
Amphetamine 
A similar dose (0.66 mg/kg body weight, cal- 
culated as free base) of dl-amphetamine sul- 
phate was administered intravenously to each 
subject in all of the experiments. The amphet- 
amine concentrations in the biological fluids 
(blood plasma, cerebrospinal and ocular fluids, 
urine, bile, gastric fluid and rumen liquor) were 
determined by a sensitive and specific gas chro- 
matographic method and the concentration of 
p-hydroxyamphetamine in urine was deter- 
mined by a colorimetric method. 
The disappearance of amphetamine from 
Table VII. — Pharmacokinetic Constants Describing the 
Distribution and Elimination of Amphetamine (1) 
Species 
(number) 
B 
(ng/ml) 
(hr) 
/3 
(hr-i) 
Vd 
(litre/kg) 
Caprine (10) 
235 
0.62 
1.118 
3.08 
Porcine (9) 
330 
1.05 
0.674 
2.23 
Equine (6) 
281 
1.39 
0.500 
2.61 
Lapine (4) 
333 
1.40 
0.498 
2.29 
Avian (8) 
438 
2.27 
0.305 
1.81 
Canine (11) 
263 
4.60 
0.159 
2.67 
Feline (6) 
401 
6.53 
0.108 
1.83 
plasma was a first-order process in all species 
(Figure 4). Plasma half-lives of 0.62, 1.05, 1.39, 
1.40, 2.27, 4.49 and 6.53 hours were found in 
goats, swine, ponies, rabbits, chickens, dogs and 
cats respectively, Table VII. The mean biological 
half-life of this drug in these randomly selected 
groups of animals varied significantly between 
species (F-test, p<0.01). No sex difference in 
5CX)i 
2 3 4 
TIME IN HOURS 
Figure 4. — Disappearance of amphetamine from the 
blood plasma of several species following the intrave- 
nous injection of amphetamine sulfate (0.66 mg/kg, 
calculated as free base) . 
