The effect of carbamazepine on the 2-hydroxylation of desipramine.

The effect of carbamazepine (CBZ, 200 mg twice daily for 28 days) on the kinetics of a single oral dose of desipramine (DMI, 100 mg) was investigated in six healthy volunteers. Compared with a control session, treatment with CBZ caused a marked increase in DMI apparent oral clearance (from 1.05 +/- 0.40 to 1.38 +/- 0.52 1 h per kg, means +/- SD, P < 0.01) and a significant shortening in DMI half-life (from 22.1 +/- 3.5 to 17.8 +/- 3.5 h, P < 0.01). The amount of 2-hydroxydesipramine (2-OH-DMI) excreted in urine over a 24-h period was significantly increased during CBZ intake (from 75 +/- 15 to 92 +/- 16 mumol, P < 0.01). These findings suggest that CBZ induces the 2-hydroxylation of DMI, a reaction primarily catalyzed by the polymorphic CYP2D6 isozyme. This interaction may have considerable practical significance.