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Unable to capture Absorption & elimination phase #81

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anujadhas opened this Issue Oct 12, 2017 · 5 comments

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anujadhas commented Oct 12, 2017

Hello,
I am dealing with one formulation where I am not able to captureAbsorption & elimination phase.
Can I get some hint which parameters should be modified?

Here I am attaching picture of simulation of plasma profile.

capture

@msevestre msevestre added the question label Oct 12, 2017

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tobiasK2001 Oct 17, 2017

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Dear Anujadhas,

Sorry it is a bit hard for me to answere your question from the info provided.
The reasons for the mismatch ob simulation and data can be manifold. What did you try so far? Were you able to describe the compound in another formulation? If yes which? Did you follow the way pointed out this best practice?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080648/pdf/PSP4-5-516.pdf
Hope this might help you!

Best, Tobias

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tobiasK2001 commented Oct 17, 2017

Dear Anujadhas,

Sorry it is a bit hard for me to answere your question from the info provided.
The reasons for the mismatch ob simulation and data can be manifold. What did you try so far? Were you able to describe the compound in another formulation? If yes which? Did you follow the way pointed out this best practice?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080648/pdf/PSP4-5-516.pdf
Hope this might help you!

Best, Tobias

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anujadhas Oct 17, 2017

Hello Tobias,

I am dealing with Extended Release formulation (Animal study: Beagle) having,
T1/2: 3 hrs
Lipophilicity: 3.4
Fraction Unbound: 42%
Metabolized by CYP1A2

I can't share all details as it is Confidential.

I am not at all able to capture absorption and elimination. This is my first attempt of M&S, So I don't have any idea which parameters need to be adjusted/modified.

anujadhas commented Oct 17, 2017

Hello Tobias,

I am dealing with Extended Release formulation (Animal study: Beagle) having,
T1/2: 3 hrs
Lipophilicity: 3.4
Fraction Unbound: 42%
Metabolized by CYP1A2

I can't share all details as it is Confidential.

I am not at all able to capture absorption and elimination. This is my first attempt of M&S, So I don't have any idea which parameters need to be adjusted/modified.

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msevestre Oct 18, 2017

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@anujadhas
I agree with @tobiasK2001 that following the PBPK modeling best practices as described in the aforementioned article would be the way to go, especially if you have no experience with this type of simulation.

Do you have IV data? Then start with this model first to understand distribution and clearance processes. Once you have a good understanding and the IV model describes your data, It's time to look at absorption and PO models.

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msevestre commented Oct 18, 2017

@anujadhas
I agree with @tobiasK2001 that following the PBPK modeling best practices as described in the aforementioned article would be the way to go, especially if you have no experience with this type of simulation.

Do you have IV data? Then start with this model first to understand distribution and clearance processes. Once you have a good understanding and the IV model describes your data, It's time to look at absorption and PO models.

@msevestre msevestre added the answer label Oct 18, 2017

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anujadhas Oct 23, 2017

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I have oral data.

anujadhas commented Oct 23, 2017

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I have oral data.

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msevestre Apr 14, 2018

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@anujadhas Closing. Please let us know if you have any more questions

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msevestre commented Apr 14, 2018

@anujadhas Closing. Please let us know if you have any more questions

@msevestre msevestre closed this Apr 14, 2018

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