Physicochemical and drug-delivery considerations for oral drug bioavailability

The bioavailability of a compound after oral administration is a function of molecular characteristics, dosage form design, and the barrier functions of the organism. The extent of intestinal absorption is dependent on drug stability, solubility and permeability. First-pass elimination can be effected by intestinal mucosal or hepatic processing. Biological availability is dependent on the physicochemical parameters of the drug, including molecular weight and lipophilicity, as well as on specific structural features such as H-bonding capacity. This review illustrates the relationships between physicochemical parameters, intestinal permeability and hepatic processing, using a set of eight peptidomimetic renin inhibitor analogs. Results from these studies provide suggestions for the design of compounds with improved bioavailability.