Chapter 30. Inhibition of Cytochrome P-450 and Implications in Drug Development

摘要: Publisher Summary For drug development, it is desirable to develop new candidates that are not potent cytochrome P-450 inhibitor and readily inhibited by other drugs avoid potential drug–drug interaction. However, in reality, interaction mutual inhibition between almost inevitable. The polysubstrate nature of P-450s responsible for large number documented interactions associated with the inhibition. Whenever two or more administered concurrently, possibility exists. Inhibition metabolism because competing same enzyme may result unanticipated undesirable elevations plasma concentrations. Thus, enzymes clinical importance both therapeutic toxicological reasons. This chapter discusses mechanisms their implications development. In general, a significant occurs only when compete metabolic reaction major elimination pathway. definitive assessment role an individual given pathway essential determining predicting interactions. To identify isoforms oxidative drugs, general strategy has emerged vitro studies. involves use selective inhibitors, immunoinhibition, catalytic activity complementary DNA (cDNA)-based vector systems, purified enzymes, correlation markers known isoforms. Each approach its advantages disadvantages combination approaches usually required accurately isozyme drug. With recent advances technologies advent analytical techniques, now possible systems predict vivo .