716 
PHARMACOLOGY 
monium-"C with carrier was administered and 
the drug concentrations in biological samples 
were determined by radioassay. 
Protein Binding 
The extent of plasma protein binding of the 
various drugs was determined by equilibrium 
dialysis. Isotonic phosphate buffer, pH 7.4, con- 
taining or labeled drug was dialysed 
against an equal volume of plasma for 16 hours 
at 37° C. Aliquots of plasma and buffer were as- 
sayed for radioactivity. Protein concentrations 
were measured by refractometry. 
Calculations 
Values for the Y-intercept (Co) of the curves 
depicting drug disappearance and the slopes of 
these curves were determined from the drug 
concentrations in plasma, as a function of time, 
by a procedure for fitting an exponential curve 
utilizing a Wang electronic calculator with card 
programmer. The computation of the kinetic 
constants was made with the equations de- 
scribed by Doluisio and Swintosky.^^ 
RESULTS 
Figure 1 shows the mode of plasma decay of 
salicylate in each of the species studied. Disap- 
pearance followed first-order kinetics through- 
out the entire period studied in ponies, goats 
and cats ; and for the first eight hours in swine 
and dogs. The reason for the increased disap- 
pearance rate between 8 and 24 hours in the 
dog and pig was not apparent but was probably 
a manifestation of saturation kinetics. 
Table I illustrates m.ean values for the kinetic 
constants for each of the species studied. A tre- 
mendous variation in rates of disappearance 
was noted among the species. Apparent specific 
PloMTio Sol Icylote 
mg/lOO ml 
Figure 1. — Disappearance of salicylate from the blood 
plasma of several species following the intravenous 
injection of sodium salicylate (44 mg/kg). Each 
point represents the mean concentration and the 
number in parentheses is the number of animals 
studied. 
volumes of distribution suggest that salicylate 
was confined largely to the extracellular space 
in the species studied. The low value for Vd in 
the goat is believed to illustrate the error in 
dosage introduced by the weight of the rumen 
and its contents. It is apparent from Co that the 
dose administered to goats produced an extraor- 
dinary plasma level as compared to the other 
species. The rumen and its contents comprise 
approximately 25 % of the body weight and ap- 
parently were not included in the volume of dis- 
Table I. — Comparison of Kinetic Constants for the disappearance of Salicylate from the Blood Plasma of Several 
Species 
Species 
No. 
Mean Wt. 
Mean Dose" 
Co 
Vd 
Vd 
kd 
TVz 
kg 
mg 
mg/100 ml 
L 
L/kg 
hr-i 
hr 
Cat 
10 
2.3 
89.4 
18.6 
0.48 
0.209 
0.018 
37.6 
Dog 
7 
8.B 
322 
20.0 
1.61 
0.189 
0.081 
8.6 
Swine 
10 
120.3 
4661 
21.3 
21.37 
0.178 
0.118 
6.9 
Pony 
14 
197.0 
7466 
21.1 
36.33 
0.180 
0.673 
1.0 
Goat 
11 
41.1 
1556 
29.3 
5.31 
0.129 
0.884 
0.8 
' Calculated as the free acid. Co = plasma concentration of drug at zero time. Vd = apparent volume of distribution. Vd = apparent spe- 
cific volume of distribution. Kd = apparent first-order disappearance rate constant. T % = half-life of drug in plasma. 
