724 
PHARMACOLOGY 
CHLOUMPHEmCOL IV 
30i 
Table XII. — Kinetic Constants for the Disappearance 
of Chloramphenicol from the Blood Plasma of Do- 
mesticated Animals 
TIKE IN HOURS 
Figure 6. — Disappearance of chloramphenicol from 
the plasma of several species following the intrave- 
nous injection of chloramphenicol (22 mg/kg). Each 
point represents the mean value from eight animals. 
all species and distribution equilibrium was at- 
tained rapidly (less than 30 min.) . 
Values for the kinetic constants are given in 
Table XII. The half-life of the drug in the 
plasma was longest in cats and shortest in pon- 
ies. Values for V'd varied among species and 
were large (in excess of total body mass). This 
indicates that chloramphenicol, like the other 
bases studied, is sequestered in the tissues. This 
drug was unusual in that the cat had the largest 
specific volume of distribution while that in the 
ruminant was much less. 
Table XI. — Kinetic Constants for the Disappearance of 
Pentazocine from the Blood Plasma of Various Spe- 
cies of Domestic Animals 
Co 
T% 
k'd 
Vd 
Species 
mg./L. 
(min.) 
L.Ak. 
Ponies 
0.69 
97.1 
0.0071 
5.09 
Goats 
0.52 
51.0 
0.0136 
5.77 
Swine 
0.63 
48.6 
0.0143 
4.76 
DOSB 
0.85 
22.1 
0.0313 
3.66 
Cats 
1.08 
83.6 
0.0083 
2.78 
Co is the value for plasma concentration of drug at zero time. 
TVs is the plasma half-life. 
k'd is the apparent first-order disappearance rate constant. 
V'd is the apparent specific volume of distribution of the dm?. 
Co 
Kd 
V'd 
V'd* 
Species 
(mg/L) 
(hrs) 
(hr-i) 
LAg 
L/kg. 
Dogs 
12.4 
4.2 
0.24 
1.77 
2.96 
Cats 
9.S 
5.1 
0.14 
2.86 
3.69 
Swine 
21.0 
1.3 
0.63 
1.05 
1.61 
Goats 
16.5 
2.0 
0.35 
1.33 
1.91 
Ponies 
21.5 
0.9 
0.77 
1.02 
1.46 
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. V'd* = Apparent specific volume 
of distribution corrected for protein binding. 
Results of the study of extent of chloram- 
phenicol-plasma protein interaction are summa- 
rized in Table XIII. All determinations were 
made at an initial drug concentration of 20 
[xg/ml. Values varied from 30.1% in the goat to 
46% in human plasma. The variation observed 
among the various species probably is due to 
species differences in albumin because there 
was no relationship between extent of binding 
and protein concentration. The effect of drug 
concentration on the extent of binding of chlor- 
amphenicol was studied in feline, canine, 
equine, caprine, porcine and human plasma at 
drug concentrations of 10, 20, 40, 60 and 100 
jUg/ml. Within this range the extent of binding 
was independent of drug concentration. Accord- 
ingly, we could correct the values calculated for 
V'd to obtain the V'd for free drug. These val- 
ues for the various species are listed in Table 
XII. 
Chloramphenicol in gelatine capsules was 
given orally (10 mg/lb) to each animal. The 
time course of drug concentration in plasma are 
shown in Figure 7. Peak levels occurred at two 
hours in swine and dogs and at three hours in 
ponies and cats. Detectable concentrations of 
chloramphenicol in the blood of goats were not 
Table XIII. — Extent of Chloramphenicol-Plasma 
Protein Binding 
Species 
Drug Bound to 
Plasma Protein (%) 
Plasma Protein 
Concentration g/100 ml 
Dog 
39.5 ± 3.4 
8.1 ± 0.16 
Cat 
37.7 ± 2.1 
7.9 ± 0.25 
Swine 
35.1 ± 2.5 
6.0 ± 0.16 
Goat 
30.1 ± 2.6 
7.8 ± 0.34 
Pony 
30.4 ± 2.0 
8.7 ± 0.19 
Human 
46.0 ± 0.46 
8.1 ±. 0.24 
Values 
are expressed as the means ± 1 
S.E.M. 
