I have a drug that has poor bioavailability I am trying to determine luminal drug contration time profile in different segements of GI tract. Is there any way we can predict or simulate drug concentrations in GI tract segemetns based on the blood concentration time profile and/or physicocehmical properties of the drug. Thanks, Prasad Tata
This is a complicated problem and you will need to augment the plasma data with good in vitro or in silico data to address it. In the literature you can find references to the ACAT (Advanced Compartmental Absorbtion and Transit, Yu et al) and ADAM (Advanced Dissolution Absorption Metabolism, Masoud et al) models. The ADAM model is implemented in SimCyp (Certara) software, but you can also write the equations and provide parameters for this model using WNL. The challenge is to separate the dynamics of absorption, metabolism and distribution from the GI tract. If you only have plasma data, you can’t tell if the low bioavailability is due to one or a mixture of these. Having some data on the expected metabolism and absorption rates (from in vitro data or in silico predictions) as well as fecal excretion and urine collection can help a lot to understand the dynamics and isolate the concentrations (lumen) that you are interested in.