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allometric scaling in pksim #120
I was curious about how the scaling of a typical individual physiologic parameters is done in pksim. I traced back the literature to an excellent paper by Willmann et al in 2007 that states that allometric scaling is being adopted. For example, scaling of organ weights (OW) follows:
OW_target = (Height_target/Height_mean)^0.75 * OW_mean
From what I understood, the Height_mean and OW_mean belong to a mean adult individual. So for example, the liver weight for a 5 year old with a height of ~109 cm would be:
The thing is that when I apply this equation, the organ weights I get are way off the values mentioned in the measured ICRP database. Also, the results I get from the equation are very different than the results I get from the generated individuals in pksim. Furthermore, the generated results from pksim agree well with the ICRP data for some parameters but differ greatly for others.
So, I guess the short version of my question is: how is the scaling done in pksim?
Thanks and regards,
Thanks Stephan, Jan and Michael for your replies. The Edginton paper was very helpful in explaining some of the discrepancies between organ volumes/weights reported in ICRP and those calculated by PKSim. Nevertheless, it still doesn't explain why a scaling method based on weight or BSA wasn't adopted instead of a clearly erroneous height scaling method.
PK-Sim is not using 1.8 and 176 all the time (Mean Liver weight and mean height for adult 30 years old ICRP).
Instead, PK-Sim used the mean liver weight and mean height for a randomly generated input age.
In the case of a population, here is what's happening:
That means that the scaling with height will be pretty accurate and very close to the ICRP data by construction
Hope this clarifies things,
Thanks a lot Michael for the clarification. I guess my last question here is: because ICRP lacks the organ specific data (volumes and flows) for every possible age, what kind of extrapolation do you do for covering these gaps? In the Edgington paper mentioned in Jan's comment, it is mentioned that cubic splines were used for some parameters as blood volume and heights, so is the same extrapolation used for organ volumes?