Hydroxylation of desmethylimipramine: dependence on the debrisoquin hydroxylation phenotype

The 2-hydroxylation of desmethylimipramine (DMI) was studied in 14 healthy subjects previously phenotyped with respect to debrisoquin hydroxylation. After a single oral dose (25 mg), slow hydroxylators of debrisoquin had significantly lower total and metabolic clearances and longer plasma half-lives of DMI and excreted less 2-hydroxydesmethylimipramine than did rapid hydroxylators. These findings strengthen the hypothesis that the hydroxylations of debrisoquin and DMI may be under common enzymatic control.