ABSTRACT
Human CYP2D6 is largely noninducible but it is subject to inhibition by a large number of compounds including therapeutic drugs and other substances. This is one of the most possible reasons for many clinically observed drug–drug interactions when the victim drugs are mainly metabolized by CYP2D6. The drug–drug interaction involving CYP2D6 may be minor, mild, or fatal. When the elimination of the victim drugs is compromised by CYP2D6 inhibition, drug response may be altered and adverse drug reactions (ADRs) may occur. For example, CYP2D6-mediated venlafaxine–propafenone interaction may cause hallucinations and psychomotor agitation (Gareri et al. 2008). Combined use of serotonergic agents that are substrates of CYP2D6 can also cause severe ADRs. So far, a number of endogenous compounds and xenobiotics are identified as CYP2D6 inhibitors with different inhibitory profiles and mechanisms (Table 4.1). This chapter will discuss the inhibitor selectivity of CYP2D6 and the clinical implications.
