Role of pharmacokinetics in the discovery and development of indinavir

The discovery of indinavir is a successful example in which pharmacokinetic and metabolic information were incorporated into drug design. The use of animal and in vitro human metabolic data in predicting the oral bioavailability and hepatic clearance in humans was critical in selecting indinavir as a drug candidate for development. In its development stage, pharmacokinetics continued to play an important role in identifying the key properties of indinavir in vivo, which allowed the characterization and prediction of the time course of drug action under physiological and pathological conditions. This review describes the role of pharmacokinetics and drug metabolism in the discovery and development of indinavir.