L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
721 
tive of extensive tissue distribution and seques- 
tration of the drug. The corrected V'd values 
are of theoretical interest in that they represent 
the apparent specific volumes of distribution for 
the respective species if all of the drug in the 
blood plasma v^ere freely diffusible, i.e., not 
bound to plasma protein. 
Results of the study of plasma protein bind- 
ing are summarized in Table X. The extent of 
quinidine-protein binding varied inversely v^^ith 
drug concentration in all species. Species differ- 
ences in the extent of protein binding of drug 
were observed. Quinidine v^^as bound least in 
caprine plasma (77%) and most in porcine 
plasma (98%) at a drug concentration of 
5/ag/ml. Values for the extent of binding in the 
plasma of other species studied w^ere intermedi- 
ate betv^een these two extremes. 
The pattern of species differences in the ki- 
netic constants for quinidine differed somev^hat 
from patterns for other bases such as amphet- 
amine, pentazocine, and chloramphenicol. The 
half-lives of quinidine vi^ere similar in sv^^ine 
and dogs (about 5.5 hrs.), somev^^hat shorter in 
ponies (4.4 hrs.) and much shorter in cats (1.9 
hrs.) and goats (0.85 hrs.). The explanation for 
these species differences in rate of disappear- 
ance of quinidine is obscure at the present time 
but probably is a manifestation of differing 
rates of biotransformation. The principal path- 
way for biotransformation of quinidine is hy- 
Table IX. — Kinetic Constants for the Disappearance of Quinidine from the Blood Plasma of Domesticated Animals 
Species 
Co 
(mg./L.) 
T Vz 
(hr.) 
kd 
(hr.-i) 
V'd 
(L./kg.) 
Corrected V'd 
(L./kg.) 
Ponies 
0.83 ± 0.11 
4.37 ± 0.36 
0.16 ± 0.015 
6.32 ± 0.71 
34.0 
Goats 
2.68 ± 0.73 
0.85 ± 0.08 
0.82 ± 0.080 
4.89 ± 0.94 
16.3 
Swine 
9.69 ± 1.88 
5.42 ± 1.56 
0.13 ± 0.031 
1.25 ± 0.29 
49.5 
Dogs 
3.56 ± 0.33 
5.59 ± 0.83 
0.14 ± 0.016 
2.91 ± 0.23 
22.0 
Cats 
4.65 ± 0.41 
1.87 ± 0.28 
0.40 ± 0.056 
2.22 ± 0.20 
21.5 
Co = plasma concentration of drug at zero time. T % = plasma half-life, kd = apparent first-order disappearance rate constant. V'd = ap- 
parent specific volume of distribution of the drug. Corrected V'd is the apparent specific volume of distribution of free drug after correction 
for plasma protein binding. Values are reported 
as the mean ± 
S.E.M. 
Table X.- 
— Effect of Drug Concentration on 
the Extent of Quinidine-Plasma Protein Binding In Vitro 
Species 
Quinidine Concentration 
(fig/m\.) 
Protein 
Concentration 
5 
10 
25 
50 
(g./lOO ml.) 
Ponies 
82 ± 0.8 
69 ± 3.7 
63 ± 5.7 
56 ± 3.5 
6.88 ± 0.61 
Goats 
77 ± 6.9 
72 ± 7.7 
67 ± 7.5 
67 ± 5.3 
5.98 ± 0.58 
Swine 
98 ± 2.1 
85 ± 2.5 
70 ± 6.6 
61 ± 6.2 
6.48 ± 0.86 
Dogs 
87 ± 5.4 
75 ± 1.4 
72 ± 2.9 
66 ± 3.5 
5.53 ± 0.58 
Cats 
90 ± 5.8 
85 ± 9.3 
69 ± 7.5 
58 ± 4.4 
7.63 ± 0.48 
Human beings 
89 ± 7.9 
82 ± 7.3 
71 ± 7.9 
69 ± 6.7 
6.83 ± 0.10 
Values for the extent of binding of drug are expressed as the mean p ercent bound ± S.E.M. 
Figure 5. — Disappearance of quinidine from the blood 
plasma of several species following the intravenous 
injection of quinidine hydrochloride (10 mg/kg, cal- 
culated as free base). Ponies were given a dose of 5 
mg/kg. Each point represents the mean drug concen- 
tration and each vertical bar equals ± 1 S.E.M. 
