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I have some problems answering the question whether animal data are scaleable to predict human
concentration time profiles or not.
I have data from three different species plus human data at different dosing levels. My first
problem is that data seem to violate dose proportionality assumption (which means that prediction
within each species is not possible). So I think that my only option is to go on with the lowest
dose levels and assume dose proportionality only for these levels. Or can I use all data for my
I like the concept of physiological time and the complex dedrick plot as a graphical tool for the
ability of data to predict human parameters. I generated a complex dedrick plot like it is described
in Mahmood (2005), Interspecies Pharmacokinetic Scaling, page 226, using only the lowest dosing
levels per animal species. The three curves are far away from overlapping, so can I conclude that my
animal data can not be used for the predictation in humans as other between-species factors than
physiological time exist?
How can I predict PK parameters (e.g. Clearance) in man using the complex dedrick plot based on the
three animal species data to check the observed human parameters with the predicted?
Does anyone know the difference between the complex dedrick plot of Mahmood (2005) using simple
allometric scaling for the exponents of clearance and volume of distribution and the complex dedrick
plot of Gabrielsson and Weiner (2000), Pharmacokinetics and Pharmacodynamics, page 732, using a
complex pharmacokinetic model for the estimation of the exponents of clearance and volme of
If someone has any hints or comments regarding my analysis or my scope I would be very happy to hear
Thanks for your help!
[Maybe you should explore the departure from dose linearity between animals of the same species
first. If it is metabolism related it may be difficult to 'scale' between species - db]
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If the dose proportionality assumption doesn't hold within a single
species, chances are the pk is nonlinear. I could be wrong but I think
dedrick plots work for linear pk scenarios.
[A reference that might be useful -
Boxenbaum, H., & Ronfeld, R. (1983). Interspecies pharmacokinetic scaling and the Dedrick plots. The
American journal of physiology, 245(6), R768–75. - db]
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