I'm trying to validate Caco-2 monolayers grown in transwells, to later perform biowaiver of new drugs. The next objective is to estimate the apparent permeability coefficient (Papp) of 13 drugs suggested by FDA for this purpose. Some colleagues have suggested me to use concentrations (cc) similar to intestinal cc reached after oral formulation of these drugs are taken orally. This data is almost impossible to find. Someone knows a rational way to establish cc to use, without making a cc screening for each drug??
Hi Tullio,
In our lab we use the following formula to come across a concentration to which intestinal cell might be exposed.
CC= Drug dose (mg)/Gut volume (mL).
Although this is not a perfect formula to derive a cc, but due to practical constraints we follow it.
Looking forward to read expert comments on this topic.
Cheers!
Rohitash
Hi Rohitash,
Many thanks for the suggestion.
Is the gut volume that you use 250ml approximately?.
Do you know where can I find the -highest dose strength- value of several drugs so to perform CaCo-2 validation?
Cheers.
Matías
We use a gut volume of 1000 mL (again an approximation as there is no consensus on the gut volume in published literature). For dose strength I would suggest going through published clinical data for particular drug or refer to the drug dossier.
I think you might get your highest dose strength at the link below (Maximum Recommended Therapeutic Dose (MRTD) Database from FDA)
http://www.fda.gov/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/ucm092199.htm
I think the best way is to screen for the strength is do the MIC (minimum inhibitory concentration) test.
Good luck
- Badges
- Science topic