L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
723 
to investigate analgesic efficacy although the 
subjects seemed to tolerate the blood collection 
procedures better after the absorption of the 
drug. 
Pharmacokinetics. The modes of absorption 
and disappearance of pentazocine from the 
blood plasma of the various species v^ere stud- 
ied. Peak plasma levels of pentazocine occurred 
at 15 minutes in dogs, goats and sv^^ine; at 30 
minutes in ponies and at 1 hour in cats. Disap- 
pearance of the drug from plasma followed 
first-order kinetics in all species except dogs. A 
biphasic mode of disappearance was noted in 
canine subjects. A rapid fall in pentazocine con- 
centration (TVi — 22 minutes) occurred be- 
tween 15 minutes and 1 hour. This was fol- 
lowed by a slower (TV2 — 150 minutes) rate of 
decay from 1 hour through 7 hours. 
Values for kinetic constants are tabulated in 
Table XI. The plasma half-life was shortest in 
dogs and longest in ponies. On extrapolating to 
zero time, the mean values for Co (drug concen- 
tration at zero time) varied from 0.52 mg/L in 
goats to 1.08 mg/L in cats. Values for V'd (ap- 
parent specific volume of distribution) were in- 
dicative of extensive tissue distribution and se- 
questration of the drug. 
Several effects observed following the admin- 
istration of pentazocine were similar to certain 
actions of morphine. Pollakiuria, mydriasis, sia- 
losis and emesis are common to both drugs. The 
mechanism of the polypnea in swine and ponies 
is uncertain but morphine-induced panting has 
been attributed to an alteration in the equilib- 
rium point of the hypothalamic heat-regulatory 
mechanism. The reason for the lack of overt 
drug effects in the goats is obscure but I have 
had similar experience with morphine in this 
species. 
In general, the duration of the depressant ac- 
tion of pentazocine in the various species coin- 
cided well with the persistence of plasma levels. 
However, depression persisted for a longer time 
in dogs and a shorter time in ponies than one 
might anticipate on the basis of disappearance 
of the drug from the plasma. A period of de- 
pression longer than the presence of plasma lev- 
els of pentazocine could be explained by the ob- 
servation in cats that brain concentrations of 
the drug were slightly higher than blood con- 
centrations. 
The plasma half-life of pentazocine was 
shorter than that reported in man for all of the 
species studied. These differences are most 
likely related to species differences in rates of 
metabolism. The half-life of pentazocine in cats 
was intermediate between that of morphine 
(3.05 hours) and meperidine (42 minutes). 
Similar comparisons cannot be made in the 
other species because of lack of information. 
Pentazocine rapidly left the blood and con- 
centrated in tissues. This is typical of the body 
disposition of basic amines. At peak plasma lev- 
els, assuming a blood volume of 7 % of the body 
weight, only 1.7, 1.0, 1.0, 1.0 and 1.2% of the 
dose was present in the blood of cats, dogs, 
swine, goats and ponies, respectively. The se- 
questration of the drug in the body tissues is 
further supported by a consideration of the ap- 
parent specific volumes of distribution. These 
varied from 2.78 L/kg in the cats to 5.77 L/kg 
in the goats. The higher values found for the 
herbivorous animals could be related to diffu- 
sion and concentration of the drug in the rumen 
of the goat or large colon of the pony. Ferrari^^ 
found that pentazocine concentrated in muscle, 
liver and the gastrointestinal tract of cats. 
The dose of pentazocine employed in this in- 
vestigation (3 mg/kg) was higher than that 
studied in human patients (0.6 mg/kg). The 
dose employed was well below the amount re- 
ported to produce toxicity in animals. As ex- 
pected, the peak blood levels obtained in all 
species, except cats, were nearly five times the 
concentrations observed by Berkowitz et al." 
in their human subjects. The higher plasma 
drug concentration observed in the cats was at- 
tributed to a smaller specific volume of distribu- 
tion. 
Chloramphenicol 
Chloramphenicol was studied in ponies, 
goats, swine, dogs and cats following intrave- 
nous, intramuscular and oral administration 
(10 mg/lb). The disappearance of chloram- 
phenicol from the blood plasma of the various 
species following IV administration is shown in 
Figure 6. First-order kinetics were followed in 
