Bioequivalence and Bioavailability Forum

Hi mittyri,

❝ You know MR is a nightmare for ka modelling […]. For that particular case absorption was modelled with a transit compartments chain. So there's no simple Ka to compare...

OK, clearer now. Keep in in mind that CL, V, rate constants belong to the – purely empiric – (Pop)PK concept.
I think that when you wrote

❝ ❝ ❝ ❝ ❝ We know that the kidneys do not care about lineage of entity.

you fell into this trap.

There are no organs associated with any of the PK parameters.* See also this post and read the heated debates of the two churches at David Bourne’s PKPD-list.
You have models describing IR and MR. Don’t worry about ‘differences’ in CL/V. Since CL/V in both models are purely empiric and have no connection to physiology at all, be happy and go ahead. If you are interested to explore what’s going on, IMHO, the only way out would be PBPK – which is not another league but another sport.

Remember that all models are wrong;
the practical question is
how wrong do they have to be to not be useful.   George E.P. Box

❝ ❝ ❝ […] due to low absorption rate by time unit the PK properties […] could be closer to some low dose IR (where non-linear kinetics rules). Is that correct?

I don’t think so. Generally it is the other way ’round. Nonlinear PK at high concentrations (due to saturation) gets linear at low ones. Think about C₂H₅OH.

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• Oral diclofenac follows a simple one-compartment model with a lag-time. When I had pain in my right knee, I tried hard to convince my synovia, ligaments, and cartilage that my body is a well - stirred beaker. Unfortunately the message didn’t get across.