L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
729 
OXYPHENBUTAZONE 25mg/kg 
Table XIV. — Kinetic Constants for the Disappearance 
of Tetraethylammonium from the Blood Plasma 
Figure 15. — Disappearance of oxyphenbutazone from 
the plasma of several species following intravenous 
injection (25 mg/kg). 
/xCi/Kg). This drug was of interest to us be- 
cause it is not metabolized, is a strong base 
which is completely ionized at physiologic pH 
and is highly polar. Dogs, cats and goats were 
chosen because for most of the drugs studied 
previously, these species represented extremes 
for the kinetic constants, i.e., most drugs were 
most slowly eliminated from cats, most rapidly 
eliminated from goats while the dogs were in- 
termediate. 
Elimination of this drug was first-order in all 
three species. The time-concentration profile for 
TEA in all three species is illustrated in Figure 
19. It may be observed that it required longer 
for distribution equilibrium to be attained in 
the goat than in the dog. 
The kinetic constants for TEA are tabulated 
in Table XIV, Differences in the rate constants 
(Kd and TV2) were not significant among spe- 
cies. Values for Co and V'd were not significant 
between the dog and cat. These values in the 
dog were significantly different (P < 0.05) 
from the goat and in the cat they were highly 
Co 
TI/2 
Kd 
V'd 
Species 
(mg/L) 
(hr) 
(hr- 
1) 
(L/kg) 
Cats 
9.9 ± 0.60 
0.76 ± 
0.06 
0.94 ± 
0.05 
1.0 
± 0.08 
Dogs 
6.9 ± 1.50 
0.94 ± 
0.10 
0.76 ± 
0.08 
1.6 
± 0.26 
Goats 
2.8 ± 0.38 
0.99 ± 
0.09 
0.73 ± 
0.06 
4.0 
± 0.74 
Co = plasma concentration of drug at zero time. T% = plasma 
half-life. Kd = apparent first-order disappearance rate constant. 
V'd = apparent specific volume of distribution of the drug. Values 
are reported as the mean ± S.E.M. 
different (P < 0.001 and P < 0.005) from the 
goat. 
This study would confirm that species differ- 
ences in rate of elimination of drugs are due 
largely to differences in rates of biotransfor- 
mation rather than in differences in excretory 
mechanisms. Distribution appears to have little 
influence on the overall elimination rate because 
the goat had a four-fold greater V'd than the 
cat, yet the TV2 values were essentially the 
same. 
OXYPHENBUTAZONE lOmg/kg ORAL 
O— O CATS 
• # DOGS 
U U GOATS 
O— O PONIES 
A i SWIKE 
Figure 16. — Concentrations of oxyphenbutazone in 
the plasma following oral administration (10 
mg/kg) . 
