Involvement of CYP2D6, CYP3A4, and other cytochrome P-450 isozymes in N-dealkylation reactions.

Metabolic N-dealkylation is a commonly observed biotransformation with tertiary and secondary amine drugs and related N-alkylated amides, but surprisingly little is known about the cytochrome P-450 isozymes involved in these dealkylation reactions. In this review, evidence is provided that supports the involvement of various P-450 isozymes, but especially CYP3A4 and other isozymes of the CYP3A subfamily. Although CYP2D6 is generally not considered to be capable of catalyzing the N-dealkylation of basic drugs, some examples of the involvement of this important isozyme in N-dealkylation reactions are identified. Procedures used to identify individual P-450 isozymes involved in N-dealkylation reactions are discussed.