Dan,
the initial thinking I did was in fact simplified to think first in terms of 100% permeability (in mg) being the same in;
(1) the upper small intestine,
(2) distal parts of the small intestine and the distal small intestine and
(3) proximal colon.
For a highly soluble highly permeable drug like methylphenidate formulated as modified release formulation{ Concerta} there are three such releases;
(1)drug released from the over coat on the osmotic tablet
(2) release by osmosis from within the tablet
(3) drug release within the tablet on account of the effect of the influence of water on a swellable polymer causing the drug to release.
So the amounts in mg of each of the three releases are known in this formulation are known and one can approximate the absorption time for each of the 3 releases at the different parts of the intestine.
What is not known is the ka(absorption coefficient) for each of the 3 releases. So when simulating I made various assumptions for each of the 3 ka values to see what emerged.
I compared with the observed PK profile then I iterated the assumptions on a number of occasions to get a result reasonably close to what you observe.
This is a very adhoc approach and I thought in terms of a more general simulation approach. Simulations plus I think uses transit compartments (Amidon) and the founder of the company is an aerospace mechanical engineer. I guess then I am thinking in terms of developing pml to be able to do what that program does.
Edited by Simon Davis, 08 February 2017 - 09:56 PM.
Edited formatting to make reading easier