Design principles for orally bioavailable drugs

Compound design is the hallmark of modern pharmaceutical research and development. Unfortunately, comprehensive and reliable guidelines for the introduction of favorable bioavailability properties into designed compounds remain elusive. Here, the authors discuss the limited set of design principles that address the problem of bioavailability, based on a retrospective analysis of orally bioavailable drugs. The roles of partition coefficient, molecular weight, carrier-mediated transport and conformational flexibility are evaluated. These properties are discussed as guiding principles only, and cannot be considered all-encompassing determinants of oral bioavailability.