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Advice on Fitting My Rifampin Model Better? #222

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yishuanwu opened this Issue Sep 10, 2018 · 2 comments

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@yishuanwu

yishuanwu commented Sep 10, 2018

PBPK-Rifampin.zip
Hi, I am working on building a Rifampin IV model. I am still working on fitting the adult model and have not started on the induction/inhibition processes. Ultimately, I would like to use it for neonatal DDI predictions.

I know there is a rifampin model in the template but I hope to improve on that model, and also I did not understand how it derived some of the parameters. I found a range of values in the literature for some parameters (e.g. LogP from 2.7 to 3.13, and fu from 0.125 to 0.175) and I was missing rifampin transport kinetic data. I arbitrarily set the Km of the P-gp to 1 just so I can use parameter identification to get a Vmax. I kept trying to play with each of the parameters but my model is still overestimating Cmax.

Please see the attached. RIF0 is the PK-Sim template, RIF3 is the model that I am working on. In the below images, my model is showed using dashed lines.
Adult Data

Neonate Data

@sfrechen

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sfrechen commented Sep 12, 2018

You may get some additional insights here:
https://github.com/Open-Systems-Pharmacology/Rifampicin-Model
and in our respective publication: https://doi.org/10.1002/psp4.12343

If that does not answer all your questions we are happy to give further support.

@yishuanwu

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yishuanwu commented Sep 15, 2018

Hi Dr. Frechen,
Thank you for your reply. My main concern is that the model does not seem to be describing neonatal data well, which was not part of your paper. But your paper was very insightful for me.
Shirley

@Yuri05 Yuri05 added the help wanted label Sep 20, 2018

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