BDDCS (Biopharmaceutical Drug Disposition and Classification System) divides compounds into four classes based on their permeability and solubility. This classification system is useful in predicting effects of efflux and uptake transporters on oral absorption as well as on postabsorption systemic levels following oral and intravenous dosing.
The high permeability and high solubility character of Class 1 compounds allows high concentrations in the gut to saturate both efflux and uptake transporters. Class 1 compounds may be substrates for both transporters in vitro in cellular systems, but transporter effects on absorption will not be clinically important. However, efflux transporters may have a measurable effect on the penetration of compounds through the blood-brain barrier. If systemic concentration of the compounds is lower, transporters may overcome the effect of its high passive permeability. These compounds can also be involved in transporter mediated drug-drug interactions.
Available assays for efflux transporters and blood-brain barrier penetration:
High permeability Class 2 compounds will pass through the gut membranes and uptake transporters will have no effect on absorption. However, their low solubility will limit the concentration at the enterocytes, thereby preventing saturation of efflux transporters. Consequently, efflux transporters will affect the extent of oral bioavailability and the rate of absorption of Class 2 compounds.
Availability of Class 3 compounds will be sufficient in the gut lumen due to their good solubility, but an uptake transporter will be necessary to overcome the poor permeability of these compounds. Apical efflux transporters may also be important for the absorption of such compounds when sufficient penetration is achieved via an uptake transporter.
Due to the low permeability and low solubility of Class 4 compounds, both uptake and efflux transporters play an important role in the oral bioavailability.