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Advice on Fitting My Rifampin Model Better? #222

Closed yishuanwu closed 5 years ago

yishuanwu commented 6 years ago

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 commented 6 years ago

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 commented 6 years ago

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