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DISCUSSION 
Bill Sacco, Biomedical Laboratory, Edge- 
wood Arsenal : Even though I agree with your 
paper's last statement, this is done every day. 
So, if one has to make the inferred application 
safe to humans, what method would you suggest 
at the moment? 
Dr. Davis : Well, I think it's quite discourag- 
ing. I think we were quite sanguine when we 
began this quest and the more we've learned, 
the more confusing the picture has become. If I 
had to make a judgment, I would think that the 
pig would be the most rewarding animal to look 
at. For many of these drugs, when we compare 
our values to those that are reported in normal 
humans, the pig, I think, gives the right answer 
more times than the other species. Obviously, 
the herbivorous animals are totally different in 
their handling of drugs than man. But I think 
Dr. Baggot pointed this out very well. Man 
seems to be unique, at least among the mam- 
mals that have been studied ; there's just no ac- 
counting for man as far as mechanisms for bio- 
transformation and so on. I just can't make 
generalizations at this point. It's very confus- 
ing. 
Tibor Balazs, Food & Drug Administration, 
Washington, D.C. : I would like to stretch your 
final sentence. I might go to the extreme and 
say that it is very difficult or impossible to fore- 
see the tentative behavior of a compound just 
from one individual to the other. That's what 
Dr. Cass so wisely pointed out after the pre- 
vious talk. I have had such an experience with a 
number of drugs. Let's say I could find some 
dogs with phenylbutazone plasma level which 
was as flat as the cat salicylate plasma level in 
your second slide, and another dog in which 
phenylbutazone disappearance was as steep as 
salicylate disappearance in the plasma for the 
goat, for exmple, one could only expect consist- 
ency within each animal. In a study with Dicu- 
marol, I measured biological activity (the phar- 
macologic hyperproteinemia) , and I found that 
the effects were very consistent with repetition 
of tests for each animal. 
The other aspect, as was so wisely pointed 
out, is that maybe some of these factors which 
govern the pharmacokinetic activity are subject 
to change. Let's say I can visualize that the cat 
might "learn" to metabolize a given drug in a 
different way. 
Dr. Davis : Well, I'm certainly not trying to 
indicate that we should just get out of animal 
studies as far as drugs are concerned; this is 
obviously impossible. I would simply, though, 
substantiate Dr. Brody's position. That is, in 
the course of development of new drugs, I think 
it is important to get them into the species in 
