In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral and intravenous administration.

1. Class I: Drugs with high solubility and high permeability, resulting in efficient absorption and minimal transporter influence (e.g., metoprolol, propranolol, and amoxicillin).
2. Class II: Drugs with low solubility but high permeability, where efflux transporters can significantly limit absorption and pump drugs into bile (e.g., ezetimibe, ibuprofen, and ketoconazole).
3. Class III: Drugs with high solubility but low permeability, where uptake transporters may enhance absorption (e.g., cimetidine, cephalexin, and ranitidine).
4. Class IV: Drugs with low solubility and permeability. They often exhibit poor bioavailability due to dual limitations (e.g., itraconazole, chlorothiazide, and furosemide).

By integrating solubility and permeability, the Biopharmaceutical Classification System highlights how transporters influence drug disposition; for instance, Class II drugs face significant challenges due to efflux into the gastrointestinal lumen and biliary excretion.