726 
PHARMACOLOGY 
PHENYLBUTAZONE 35nng/kg 
O O CATS 
0 # DOGS 
□ □ GOATS 
O O PONIES 
■ SWINE 
Figure 9. — Disappearance of phenylbutazone from the 
plasma of several species following intravenous injec- 
tion (3.5 mg/kg). 
The drug appeared to be readily absorbed from 
the depot site in all species. 
Phenylbutazone 
Phenylbutazone was studied in dogs, cats, 
swine, ponies and goats following I.V. adminis- 
tration (at three dosage levels — 3.5, 10 and 25 
mg/kg) and following oral administration of 10 
mg/kg. The concentration-time relationships 
are shown in Figures 9-12. The time course of 
this drug in the plasma of the various species 
was unusual in that carnivores eliminated it 
more rapidly than did the other species. Phenyl- 
butazone had a longer half-life in all of the 
species than any other drug studied. The spe- 
cific volume of distribution were somewhat dif- 
ferent in that the drug had a smaller apparent 
volume of distribution in the ruminant animal 
than in swine or ponies. Blood concentrations 
increased proportionately by increasing the 
dose from 3.5 to 10 mg/kg but a further in- 
crease from 10 to 25 mg/kg did not result in 
proportionate blood levels. 
These effects are accounted for on the basis 
of plasma protein binding of the drug. At low 
drug concentrations 10-20 mg/L the drug was 
nearly 100% bound in plasma from goats, 
swine and humans, 70% in ponies and 85% in 
dogs and cats. The extent of binding decreased 
with increasing drug concentration except in 
ponies. Drug concentration had no effect on ex- 
tent of binding in equine plasma throughout the 
range of 10 to 100 mg/L, The species differ- 
ences observed in the absorption of phenylbuta- 
zone following oral administration are difficult 
to explain. Highest peak blood levels occurred 
in goats and the lowest were attained in swine. 
Absorption was relatively slow in all species. 
The principal metabolites isolated from the 
urine were oxyphenbutazone, the glucuronide 
and ethereal sulfate of oxyphenbutazone. Spe- 
cies differences were observed in distribution of 
these compounds in 24-hour urine samples. Oxy- 
phenbutazone was the principal metabolite iso- 
lated from the urine of ponies, swine, and cats. 
The glucuronide accounted for most of the drug 
eliminated in the urine of dogs and goats. Sul- 
PHENYLBUTAZONE lOmg/kg 
to -I 
O O CATS 
m M DOGS 
D 5 GOATS 
O Q PONIES 
A S SWINE 
Figure 10. — Disappearance of phenylbutazone from 
the plasma of several species following intravenous 
injection (10 mg/kg). 
