722 
PHARMACOLOGY 
droxylation of the quinuclidine nucleus while 
hydroxylation of the quinoline ring is a minor, 
secondary pathway. 
Quinidine was unusual in our experience in 
that the cat was able to eliminate it more rap- 
idly than were swine, dogs, and ponies. The cat 
eliminated amphetamine, pentazocine, salicylate 
and oxyphenbutazone much more slowly than 
the other species. Presumably, quinidine was 
different because conjugation mechanisms were 
not involved. The rapid rate of elimination of 
quinidine from the plasma of goats was believed 
to be due to rapid diffusion and subsequent 
trapping of quinidine in the rumen. The data 
obtained from ponies are not directly compara- 
ble to those for other species because it was nec- 
essary to employ a smaller dosage (5 mg/kg) of 
the drug. 
Quinidine rapidly diffused from the blood and 
concentrated in tissues. Distribution equilib- 
rium was complete within 30 minutes. Thus the 
kinetics of quinidine could be described ade- 
quately by a one-compartment open model in all 
species. If we employ the values for Co and as- 
sume a blood volume equivalent to 7% of the 
body weight, only 1.2, 1.8, 2.5, 3.3 and 6.8% of 
the dose was in the blood of ponies, goats, dogs, 
cats, and swine, respectively after diffusion 
equilibrium was attained. The sequestration of 
quinidine by tissues was further corroborated 
by the large values obtained for apparent spe- 
cific volumes of distribution. These varied from 
1.25 L/kg in swine to 6.32 L/kg in ponies. The 
differences in apparent volumes of distribution 
and percents of dose in the blood were related to 
the extents of quinidine-plasma protein binding 
among the species. Quinidine was 98 % bound in 
swine (smallest V'd) and 82% bound in ponies 
(largest V'd). If the drug were extensively 
bound to plasma proteins there would be less 
free drug available for diffusion. Values for Co 
were inversely related to extent of protein bind- 
ing so the differences in plasma concentrations 
among species may be explained on the basis of 
protein binding. 
The nature of the interaction of quinidine 
with plasma proteins is different from that ob- 
served with amphetamine and chloramphenicol 
because extent of binding of the latter drugs 
was independent of drug concentration. The 
fact that the extent of binding of quinidine was 
inversely related to drug concentration suggests 
the presence of specific binding sites in the 
plasma proteins. Since diffusion equilibrium oc- 
curred rapidly with high tissue/plasma concen- 
tration ratios we would expect the proteins to 
have a low affinity for the drug. 
Pentazocine 
Pharmacokinetic parameters and pharmaco- 
logic effects were studied in ponies, goats, swine, 
dogs and cats. A fluorometric procedure was de- 
veloped for the assay of pentazocine were ob- 
served among the species studied. 
Cats. Mydriasis and sialosis were constant 
findings. Five out of six cats were mildly de- 
pressed from 30 minutes through four hours. 
One cat became aggressive and excited for a pe- 
riod of five hours. The subjects did not seem to 
resent the venipunctures during the period 
after injection of the drug. Recovery was un- 
eventful. 
Dogs. Profuse salivation, diarrhea, mydriasis 
and poUakiuria were prominent signs during 
the first hour. Slight depression and ataxia 
lasted for lV^-2 hours. 
Swine. Sialosis and emesis occurred in all 
swine from 1 to 2 hours after administration. 
PoUakiuria was observed in three animals dur- 
ing the first hour. Polypnea was a constant find- 
ing from 1 to 3 hours ; this was not due to am- 
bient temperature as other swine in the barn 
were unaffected. Swine were depressed from 
the first through third hours. The animal care- 
taker was of the opinion that the swine were 
more difficult to catch and handle when under 
the influence of the drug. 
Ponies. Polypnea occurred in all subjects 
from 30 minutes to 1 hour and unsteadiness of 
gait was observed from 30 minutes to 3 hours 
after administration. Fetuses in two mares 
showed increased activity from 15 minutes to 
75 minutes after injection. Both mares deliv- 
ered normal foals three weeks after the experi- 
ment. 
Goats. No behavioral or autonomic effects 
were seen. 
No other significant untoward effects were 
observed in any species. No attempt was made 
