Bioavailability Enhancement By Attenuating Presystemic Metabolism

摘要

In regards to oral bioavailability, much research and discussion have been levied against two issues: solubility and permeability. Depending on the drug molecule, its dose, and its application, release from the oral dosage form, dissolution into gastrointestinal fluids, and avoidance of precipitation may each require significant formulation efforts and strategies. Permeability is also a considerable problem for highly hydrophilic or highly hydrophobic molecules (i.e. logP values <1.5 or >5). To handle these issues better, several systems have been devised to guide drug developers. The first common one was Lipinski's "Rule of 5", followed by Amidon's"Biopharmaceutical Classification System" (widely known as BCS), Benet's"Biopharmaceutical Biopharmaceutics Drug Disposition Classification System" (BDDCS), and most recently a "refined Developability Classification System" (rDCS). Although these frameworks vary in purposes and methods, their common theme is to understand the limiting factors determining oral drug bioavailability.