J. D. BAGGOT AND L. E. DAVIS 
699 
various species? This of course is a very ap- 
parent thing. My other question concerns the 
experience with these drugs diumally and noc- 
turnally because some of these animals are not 
daytime animals; some of them are nighttime 
animals, or not specifically daytime. If we're 
talking as pharmacologists, the paper addresses 
itself to the diurnal. But I thought that it might 
be interesting to look at these experiments from 
the standpoint of the animal subject used. Of 
course in your conclusions you alluded to that. 
When one reads journals in pharmacology, a 
dog is a dog, a mouse is a mouse, and a rat is a 
rat. And those of us who have worked with 
these species recognize that the strains within 
the particular breeding colony have quite an im- 
pact on these kinds of studies and the results 
you obtain. I only speak about these things be- 
cause I feel that this is the purpose of our meet- 
ing here. 
Chairman : I appreciate your comments. Dr. 
Cass. Would you like to amplify those state- 
ments or in any way address yourself to them? 
Dr. Baggot: I'd just like to say that we did 
use a particular type of breed of animal within 
each species. We always use one breed within 
each species except for dogs. In dogs, we just 
used mongrels, randomly selected mongrel dogs. 
I do appreciate that there might be quite a dif- 
ference between breeds, particularly with the 
greyhound and the beagle. We just use these 
mongrel dogs. 
Questioner: Dr. Baggot, I'd like to just ask 
a question about the data that you have on car- 
nivorous animals. Do you think that, if you 
were to extrapolate data pertaining to urine pH 
and rate of drug excretion in these animals, this 
might have any relevance to man in terms of 
amphetamine over-dosage? Are you able to 
make any statement about that? 
Dr. Baggot: Yes, I think so. Of course in 
man it has been shown, principally by Beckett 
and Rowland, that about 30 to 40% of the am- 
phetamine is excreted unchanged in man. This 
was similar to what we obtained in the carnivo- 
rous animals. The urinary pH has a marked in- 
fluence on the half-life in the human which has 
been shown by others to be about twelve hours. 
We, too, showed urine pH to have an influence 
upon amphetamine half-life in the dog; such a 
high proportion of the dose was excreted un- 
changed. On the other hand, we showed in her- 
bivorous animals that only about 2 to 3 % of the 
dose was excreted unchanged. This implies that 
a change of urinary pH is certainly of therapeu- 
tic value in the correction of overdosage. This is 
very definite in man, of course, and in the car- 
nivorous animals. I don't think it would have 
any effect in the herbivorous species. 
Questioner: Did you go on to acidify or al- 
kalinize the urine in man ? 
Dr. Baggot: Yes, to shorten the biological 
half-life you would acidify the urine and to 
bring it down to 6.0, or somewhere below 6.0. 
Stuart Frazier, Food and Drug Administra- 
tion, Washington, D.C. : How would intrave- 
nous amphetamine half-life compare with oral 
administration? You used oral administration 
here, right? 
Dr. Baggot : No, all were administered intra- 
venously. 
Dr. Frazier: Well, how would this compare 
with the IM injection for distribution and half- 
life and so forth? 
Dr. Baggot: I never administered it other 
than intravenously, but I know that Rowland 
showed that, given orally in the human, the ab- 
sorption is very rapid. The absorption and distri- 
bution are both very rapid, being complete with, 
I think, fifteen or twenty minutes. The half-life 
should be unchanged. 
