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Hello All,
I am interested to model absorption delay of my compound (rather Tlag) using mPBPK model.
I have tried with Transit compartment modelling , but would like to be interested in exploring the
application of mPBPK model to model absorption delays (Tlag)
I have PCT data for my compound and no other tissue level data and It has been reported by Y Cao et
al that "Minimal-PBPK models offer a sensible compromise when only blood or plasma data are
available", so can anyone help me in understanding how to build this
My limitation is that ,I do not have Simcyp so unable to use that software
Regards
K.Harish Kaushik
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Both GastroPlus and SimCYP are able to model absorption delays.
The big question is why is there a delay? Maybe gastric emptying, maybe
slow dissolution, maybe the drug is a substrate for an influx transporter
that is only present in the more distal regions of the intestine (e.g.,
bile acid transporter), maybe it is a CYP3A4 substrate and with high 3A4
expression in proximal small intestine, maybe any drug that is absorbed in
that region is mostly metabolized in the gut wall and little is observed
in plasma until it is absorbed in more distal regions. There are a number
of reasons for observed "absorption delays" in drug being detectable in
plasma. Is the delay consistent across subjects? How long is the delay? Is
it observed in both fasted and fed state?
You can use a Tlag but you should try to understand why it is happening.
Best regards,
Walt
Walt Woltosz
Chairman and CEO
Simulations Plus, Inc. (NASDAQ: SLP)
and Cognigen Corp, a wholly owned subsidiary of Simulations Plus
42505 10th Street West
Lancaster, CA 93534
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