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New horizons in drug metabolism, pharmacokinetics and drug discovery.

Along with minimal toxicity, good drug metabolism and pharmacokinetic (DMPK) properties are essential for the clinical success of a drug candidate. A major cause of failure of orally administered drugs during their development is the discovery that in humans they have low intestinal absorption and/or high clearance causing low and variable bioavailability. In addition, drug interactions and the presence of active metabolites can prevent or complicate their successful development. With poor pharmacokinetics it can be difficult to achieve a suitable dosage regimen for the required pharmacodynamic action. The main role of DMPK in discovery is, therefore, the prediction of human pharmacokinetics and metabolism. Reducing the rate of attrition during drug discovery and development is now considered essential, particularly as it is now possible to screen an ever-greater number of compounds.