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Does anybody has PK-Sim Ketoconazole model to share? #103

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tobiasK2001 opened this Issue Nov 30, 2017 · 9 comments

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tobiasK2001 commented Nov 30, 2017

Dear all,
I am looking for Ketoconazole and / or Erythromycin model which I might use for a quick check. So it does not has to be the latest super sophisticated version. Pleas let me know if you have something you might want to share.

Thanks in advance! Tobias

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krinaj Mar 10, 2018

Hi Tobias,

I recently developed this attached Ketoconazole PK-Sim model. Please note different clearance rates are included for two doses (200 mg vs. 400 mg) as mentioned in Pathak et al 2017.
Ketoconazole.zip

thanks,
Krina

krinaj commented Mar 10, 2018

Hi Tobias,

I recently developed this attached Ketoconazole PK-Sim model. Please note different clearance rates are included for two doses (200 mg vs. 400 mg) as mentioned in Pathak et al 2017.
Ketoconazole.zip

thanks,
Krina

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tobiasK2001 Mar 12, 2018

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Dear Krina,

thanks for this interesting model. Just wondering, did you developed with IV data and than exprapolated the iv model to po? Or did you start with po data only? Having a closer look at it seems to me that not only the CL rates are different for the doses, but also some distribution Parameters like P (plasma ->blood cells).
Did you do some evaluation step already or are you planning to do one with e.g. multiple dose data, or DDI data?

kind regrads, Tobias

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tobiasK2001 commented Mar 12, 2018

Dear Krina,

thanks for this interesting model. Just wondering, did you developed with IV data and than exprapolated the iv model to po? Or did you start with po data only? Having a closer look at it seems to me that not only the CL rates are different for the doses, but also some distribution Parameters like P (plasma ->blood cells).
Did you do some evaluation step already or are you planning to do one with e.g. multiple dose data, or DDI data?

kind regrads, Tobias

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krinaj commented Mar 12, 2018

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tobiasK2001 Mar 12, 2018

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Dear Krina,

yes it is a good idea to fix fu values to literature. You may also have a look at this Ketomodel described here (if not already known) as it seems to by somewhat better describing the DDI data than the model which Phatak et al are using:
https://www.ncbi.nlm.nih.gov/pubmed/23584886

Hope you might find this usefull.

Best Tobias

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tobiasK2001 commented Mar 12, 2018

Dear Krina,

yes it is a good idea to fix fu values to literature. You may also have a look at this Ketomodel described here (if not already known) as it seems to by somewhat better describing the DDI data than the model which Phatak et al are using:
https://www.ncbi.nlm.nih.gov/pubmed/23584886

Hope you might find this usefull.

Best Tobias

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krinaj Mar 15, 2018

Hello,

Here is the ketoconazole model that I ended up with. It has been evaluated across a couple of DDI studies (1 for oral Midazolam, 1 for IV Midazolam), and across different dosing regimen. I am attaching a simple sim with ketoconazole model that I saved in my user templates.

Hope this helps.
Krina
Ketoconazole.zip

krinaj commented Mar 15, 2018

Hello,

Here is the ketoconazole model that I ended up with. It has been evaluated across a couple of DDI studies (1 for oral Midazolam, 1 for IV Midazolam), and across different dosing regimen. I am attaching a simple sim with ketoconazole model that I saved in my user templates.

Hope this helps.
Krina
Ketoconazole.zip

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tobiasK2001 Mar 16, 2018

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Dear Krina,

thanks a lot for this! That is a good starting point for further investigations. How dose the evalaution looks like?
Are you planning to evaluate it further with more studies from the Paper I send you?
Perhaps this could be another Publication featuring the first whole body full PBPK model with a freeware software providing improved performance over the SimCYP model. What do you think of it?.

Best, Tobias

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tobiasK2001 commented Mar 16, 2018

Dear Krina,

thanks a lot for this! That is a good starting point for further investigations. How dose the evalaution looks like?
Are you planning to evaluate it further with more studies from the Paper I send you?
Perhaps this could be another Publication featuring the first whole body full PBPK model with a freeware software providing improved performance over the SimCYP model. What do you think of it?.

Best, Tobias

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krinaj Mar 16, 2018

Hello Tobias,

How dose the evalaution looks like?

The evaluations look good and acceptable. Please note that model changed quite a bit from what I had shared last week. It has now very few parameters optimized vs. prior model.

Are you planning to evaluate it further with more studies from the Paper I send you?

I had already referred to Han et al paper that you shared before. I referred to two original DDI studies (Tsunada 1999 and Zhao 2009) mentioned in that paper. I do not plan to evaluate it further at this point.

Perhaps this could be another Publication featuring the first whole body full PBPK model with a freeware software providing improved performance over the SimCYP model. What do you think of it?.

I think it is a good idea, but I have not evaluated performance over SimCYP model. If you would like to do further evaluation and co-author a publication, I will be happy to work together. :)

thanks,
Krina

krinaj commented Mar 16, 2018

Hello Tobias,

How dose the evalaution looks like?

The evaluations look good and acceptable. Please note that model changed quite a bit from what I had shared last week. It has now very few parameters optimized vs. prior model.

Are you planning to evaluate it further with more studies from the Paper I send you?

I had already referred to Han et al paper that you shared before. I referred to two original DDI studies (Tsunada 1999 and Zhao 2009) mentioned in that paper. I do not plan to evaluate it further at this point.

Perhaps this could be another Publication featuring the first whole body full PBPK model with a freeware software providing improved performance over the SimCYP model. What do you think of it?.

I think it is a good idea, but I have not evaluated performance over SimCYP model. If you would like to do further evaluation and co-author a publication, I will be happy to work together. :)

thanks,
Krina

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StephanSchaller Mar 16, 2018

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Nice example of the OSP community collaborating:

Idea: if you actually will prepare a manuscript maybe it would be really helpful for the OSP community if you "add" the "OSP Community" in the Author list followed by you two as authors. Like e.g. the "EFPIA MI3D Workgroup" on this paper.

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StephanSchaller commented Mar 16, 2018

Nice example of the OSP community collaborating:

Idea: if you actually will prepare a manuscript maybe it would be really helpful for the OSP community if you "add" the "OSP Community" in the Author list followed by you two as authors. Like e.g. the "EFPIA MI3D Workgroup" on this paper.

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msevestre Apr 6, 2018

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Thanks @krinaj for sharing

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msevestre commented Apr 6, 2018

Thanks @krinaj for sharing

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