Re: QSAR - QSAR: Published correlations of animal versus human PK data for numerous compounds ?

Dear Jim,

Our Blood/Brain partition predictor at ChemSilico was developed on data
from male white rats. We used plasma/CSF data, the majority of which
came from Human subjects, as our external validation. This method
produced very encouraging results, given the nature of the data in
question. (see http://www.chemsilico.com/CS_prBBB/BBBexp.html)

There were some compounds where data was available from both white rats
and Humans. These duplicate values were used to evaluate the
compatibility of the data, which was determined to be good. Blood/Brain
and plasma/CSF values are not identical and, of course, neither are
Humans and rats (most of the time). We feel that the outcome of the
study indicates the utility of using data from white rats to predict
outcomes in Human patients.

This data is our own compilation and has not yet been published, but the
references are given on the web page. I do not know if this is the kind
of thing that you are looking for, but I hope it may be of help.

Please let me know if I can provide any further detail that may be of
interest.

L. Mark Hall
Hall Associates Consulting

james.metz]~[abbott.com wrote:

>
> QSAR Society,
>
> Numerous publications exist which attempt to develop QSAR models
> to predict ADMET in humans
> and other preclinical animal species. A significant component of the
> pharmaceutical industry presupposes that
> preclinical pharmacokinetics (PK) in animals is at least *somewhat*
> predictive of PK in humans.
>
> Is anyone aware of any publications which clearly show the
> correlation (or lack thereof !) between experimental
> PK data in animals and humans for more than a few compounds? For
> example, is anyone aware of any publications
> showing a plot of po %F in rats (or mice) versus po %F humans for say
> 20 - 30 (hopefully more) compounds?
>
> I am aware of publications with a few isolated comparisons.
> However, I am looking for a more definitive,
> "comprehensive" analysis. I have yet to find any !
>
> Thank you,
> Jim Metz
>
>
> James T. Metz, Ph.D.
> Research Investigator Chemist
>
> GPRD R46Y AP10-2
> Abbott Laboratories
> 100 Abbott Park Road
> Abbott Park, IL 60064-6100
> U.S.A.
>
> Office (847) 936 - 0441
> FAX (847) 935 - 0548
>
> james.metz*o*abbott.com
Received on 2003-10-15 - 12:59 GMT