INVOLVEMENT OF CYP2D6, CYP3A4, AND OTHER CYTOCHROME-P-450 ISOZYMES INN-DEALKYLATION REACTIONS

Metabolic N-dealkylation is a commonly observed biotransformation with tertiary and secondary amine drugs and related N-alkylated amides, bu t surprisingly little is known about the cytochrome P-450 isozymes inv olved in these dealkylation reactions. In this review, evidence is pro vided that supports the involvement of various P-450 isozymes, but esp ecially CYP3A4 and other isozymes of the CYP3A subfamily. Although CYP 2D6 is generally not considered to be capable of catalyzing the N-deal kylation of basic drugs, some examples of the involvement of this impo rtant isozyme in N-dealkylation reactions are identified. Procedures u sed to identify individual P-450 isozymes involved in N-dealkylation r eactions are discussed.