THE EFFECT OF SERTRALINE ON THE PHARMACOKINETICS OF DESIPRAMINE AND IMIPRAMINE

Objective: To examine the pharmacokinetic interaction between the sele ctive serotonin reuptake inhibitor sertraline and the tricyclic antide pressants desipramine or imipramine in 12 healthy male subjects. Metho ds: Participants received a 50 mg single dose of either desipramine or imipramine under three conditions: alone, after a single 150 mg dose of sertraline, and after the eighth daily 150 mg dose of sertraline. P lasma samples were analyzed for desipramine or imipramine concentratio n by HPLC with electrochemical detection, and pharmacokinetics were de termined with use of noncompartmental analysis of individual data. Res ults: Multiple-dose, but not single-dose, treatment with sertraline si gnificantly reduced apparent plasma clearance (CL/F) and prolonged the half-life of desipramine relative to baseline. These changes resulted in higher plasma desipramine concentrations, as indicated by a signif icant increase in maximum plasma concentration (C-max) and area under the plasma concentration-time curve extrapolated to infinity [AUC(0-in finity)] (22% and 54%, respectively). Both single-and multiple-dose tr eatment with sertraline significantly reduced the CL/F of imipramine. This effect was stronger after multiple predoses of sertraline, when i mipramine C-max and AUC(0-infinity) were increased by 39% and 68%, res pectively. These treatment effects were consistent between individuals . Conclusions: This pharmacokinetic interaction is likely the result o f an inhibition of CYP2D6 tricyclic metabolism by sertraline. When a t ricyclic antidepressant, such as desipramine or imipramine, is coadmin istered with sertraline, lower dosages of the tricyclic agents may be necessary to prevent elevated tricyclic levels.