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I'd like to have your expert opinion on the following problem:
Data (s.c. and i.v.) from 4 different species were used in an
allometric scaling exercise. All data were pooled and analysed using a
2 compartmental population pharmacokinetic model with a lag time
(NONMEM). Since it is well known that the interspecies variability in
the disposition of certain drugs is related to the body weight, a power
function of weight was used as allometric equation in order to
characterize the variability in all pharmacokinetic parameters, except
for the bioavailability.The issue is now whether it is acceptable to
include a power function of weighton ka and Tlag. In contrast to
clearance and volume of distribution, it is not clear how onecan
rationalize this. Has anyone have any thoughts on thismatter?
Your input is highly appreciated.
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Call me old-fashioned, but I'd suggest that you look at the data. See
if there is a relationship between these parameters and body weight, and
if so, whether it is of approximately the right form for a power function. If
so, then go ahead and fit one,
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Allometric scaling is an empirical function. I say, try it. If it
improves the fit, then keep it. Otherwise don't.
I don't think Ka will scale across species, but you should allow it to
vary for each species. I wouldn't expect it to be a constant.
F might be a function of weight. I don't know for sure. You have
larger surface area in humans but the transit times are different. In
the end it may be a wash. Again, try it and see if it helps the
goodness of fit.
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