PHARMACOKINETICS OF DESIPRAMINE COADMINISTERED WITH SERTRALINE OR FLUOXETINE

The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. C oncentrations in plasma were determined after 7 days of desipramine (5 0 mg/day) dosing alone, during the 21 days of desipramine and selectiv e serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued desipram ine administration after SSRI discontinuation. Desipramine C(max) was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versu s 23% for fluoxetine versus sertraline, respectively, relative to base line after 3 weeks of coadministration. Desipramine trough concentrati ons approached baseline within 1 week of sertraline discontinuation bu t remained elevated for the 3-week follow-up period after fluoxetine d iscontinuation. Concentrations of SSRIs and their metabolites correlat ed significantly with desipramine concentration changes (for fluoxetin e/ norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethy lsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacoki netic interaction with desipramine than did fluoxetine at their respec tive, minimum, usually effective doses.