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What pH does PK-Sim calculate specific intestinal permeability for? #25

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TatianaAlieva opened this Issue Jun 13, 2017 · 5 comments

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TatianaAlieva commented Jun 13, 2017

Excuse me, I have not found this info in the manual.
Thank you in advance!

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Yuri05 commented Jun 14, 2017

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TatianaAlieva Jun 14, 2017

Excuse me, I am asking, because I was unable to find the explicit value of pH neither in the manual nor in the paper you mentioned.

TatianaAlieva commented Jun 14, 2017

Excuse me, I am asking, because I was unable to find the explicit value of pH neither in the manual nor in the paper you mentioned.

@msevestre msevestre removed the answer label Jun 16, 2017

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KatrinCoboeken Jun 20, 2017

Per default for the permeability calculation, charge and pH value are not considered.
But it is possible to introduce a charge and pKa dependent penalty factor.
To do this, go to the parameters of a simulation, search under "permeability" the parameter: "Use pH and pKa dependent penalty factor for charged molecule fraction" and set it to "Yes".
Then an additional factor is multiplied to the intestinal permeability.

The factor is calculated as described in:
A physiological model for the estimation of the fraction dose absorbed in humans.
Willmann S, Schmitt W, Keldenich J, Lippert J, Dressman JB.
J Med Chem. 2004 Jul 29;47(16):4022-31.

KatrinCoboeken commented Jun 20, 2017

Per default for the permeability calculation, charge and pH value are not considered.
But it is possible to introduce a charge and pKa dependent penalty factor.
To do this, go to the parameters of a simulation, search under "permeability" the parameter: "Use pH and pKa dependent penalty factor for charged molecule fraction" and set it to "Yes".
Then an additional factor is multiplied to the intestinal permeability.

The factor is calculated as described in:
A physiological model for the estimation of the fraction dose absorbed in humans.
Willmann S, Schmitt W, Keldenich J, Lippert J, Dressman JB.
J Med Chem. 2004 Jul 29;47(16):4022-31.

@msevestre msevestre added the answer label Jun 21, 2017

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TatianaAlieva Jun 28, 2017

Dear Katrin,
Excuse me for keeping silence so long.
Thank you for your answer!
I'm not sure that all users are aware of pH-partition hypothesis. Why does PK-Sim not account for dissociation in the default mode? It strongly improves the predictive power.
Tatiana

TatianaAlieva commented Jun 28, 2017

Dear Katrin,
Excuse me for keeping silence so long.
Thank you for your answer!
I'm not sure that all users are aware of pH-partition hypothesis. Why does PK-Sim not account for dissociation in the default mode? It strongly improves the predictive power.
Tatiana

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msevestre Apr 14, 2018

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Closing in favor of PKSim issue #607

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msevestre commented Apr 14, 2018

Closing in favor of PKSim issue #607

@msevestre msevestre closed this Apr 14, 2018

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