Animal Populations: Goettingen Minipig

[StephanSchaller]

In a recent project, I am confronted with a number of issues with the existing PKSim Minipig model:

• The PKSim Database only represents a 40 kg Minipig, which is linearly scaled if larger or smaller pigs are required. Many labs use smaller minipigs (6 months and 14 kg BW) to economize compound usage.

• Linear scaling is of course nonsense. At least allometric scaling should be considered.

• Especially for Dose/BW experiments, linear scaling dose not introduce any variability whatsoever in the results, so populations are useless.

• Also, variability for most properties cannot be added manually in the population

• Last but not least, the model structure is not consistent with the human model, making scaling of models in MATLAB only possible with quite extensive workarounds (which I have solved but cannot be expected from a standard user)

What can we do to solve these issues (I admit, the last one should be an extra thread, I opened #378)?

[msevestre]

@StephanSchaller

Linear scaling is of course nonsense. At least allometric scaling should be considered

Can you explain how this would be done? (especially based on which data.).

[StephanSchaller]

Well, just like we developed all the other populations: literature search & implementation.

There has been a recent publication by Roche: Claudia Suenderhauf & Neil Parrott which is quite informative.

Of course, this just covers a different but narrow weight range around 14 kg. But it is a start. If you can tell me how to create and integrate new populations in PKSim I would be happy to start. But this could take a while.

[msevestre]

@StephanSchaller

Well, just like we developed all the other populations: literature search & implementation.

Thanks for the clarification.

You mentioned allometric scaling in your previous post. How would go about that (as opposed to implemented a full blown population)

[StephanSchaller]

@msevestre

You mentioned allometric scaling in your previous post. How would go about that <

It would still be a half-blown literature search: Ideally we would have for at least 3 different BWeights information on all required physiological properties

• Organ Size and properties (fraction vas/in/cell, protein/water content, endothelial surface areas... )
• Cardiac output
• ... And then you would fit an exponential scaling function (function of BW) through these 3 points for each property: sth. like c1^(k1*BW) while k1 < 1.

[OZaher]

Hello everyone. I am developing pigs PBPK models for some compounds and I faced the same issue for variability as the compounds were given in Dose/Kg which resulted in almost the same PK profile for all the pigs in the study despite being different in weight. My question here is I tried to look for the reference provided about the pig model to find explanation for this issue in the pig model but I could not , so if I can have more information about that, it will be helpful .