MAPROTILINE METABOLISM APPEARS TO CO-SEGREGATE WITH THE GENETICALLY-DETERMINED CYP2D6 POLYMORPHIC HYDROXYLATION OF DEBRISOQUINE

1 The plasma concentrations of the tetracyclic antidepressant maprotiline and its effect on histamine-induced bronchoconstriction were measured after single (50 mg) and multiple (50 mg twice daily) oral doses in healthy subjects. 2 Histamine-induced bronchoconstriction was abolished after a single dose of maprotiline and this effect persisted throughout multiple dose treatment. 3 The mean C(max) of maprotiline in six poor metabolisers (PM) of debrisoquine was 2.7-fold greater than that in six extensive metabolisers (EM) and the mean AUC(0,48 h) was 3.5 times higher. 4 The duration of the pulmonary effect of maprotiline after cessation of multiple dose treatment in EM was less than 3 weeks compared with at least 4 weeks in PM.