L. E. DAVIS, C. A. DAVIS AND J. D. BAGGOT 
733 
which they are going to be used as soon as the 
investigator can safely do so. And what I am 
thinking of is the possibility of coming up with 
a model in which we can get data comparable to 
what can be gotten by the clinical pharmacolo- 
gist in a hospital. This is what we were hoping 
to do when we started out five years ago, but we 
certainly didn't do this, I'm afraid. 
Chairman : Dr. Davis, I'd like to ask you one 
question that relates to your study and I wonder 
if you have any information on it. You have 
very clearly shown that there are species' dif- 
ference in handling of drugs in terms of plasma 
levels after administration. Have you found any 
histologic diiferences in your studies between 
species, when one looks at organ toxicity? 
The implications of my question are clearly 
related to drug testing prior to the use in man. 
We're all familiar with drugs that never got to 
the testing phase in man because in the test 
species there were histological changes in — let's 
say, the liver. Do you have any evidence that 
there are species' differences based on a higher- 
plasma concentration that perhaps should not 
be extrapolatable to man ? 
Dr. Davis : No, I think predominantly of the 
salicylates. In using our system, some or many 
of these drugs were studied chronically. For ex- 
ample, in the case of salicylates, we had animals 
that were receiving daily doses over a period of 
six months, and in no case did we see any prob- 
lem from the salicylate in the equine or the cap- 
rine species. In the case of swine, most of these 
animals were allowed to breed and go through 
to term pregnancy and so on. In the case of the 
swine we did notice that the newborn piglets 
were bleeders. If we hadn't had a good animal 
caretaker, I'm convinced many of these would 
have died at birth simply from hemorrhage. 
This has been reported in man, as a problem. In 
the case of cats, we did see toxicity and in veter- 
inary medicine this is a fairly important clinical 
problem. Unfortunately, much of the lay popu- 
lation considers aspirin to be innocuous because 
they take it by the handsfull. As soon as their 
cats get sick, they start giving them aspirin and 
then the veterinarian has trouble. 
