Abstract
The combination of selective serotonin reuptake inhibitors with tricyclic antidepressants has proven useful in treatment-resistant depression but has the potential for adverse drug-drug interactions. In the present study, the metabolism of a single dose of imipramine was studied before and after treatment with paroxetine. Paroxetine induced significant elevations of approximately 50% in half-life, area under the curve, and Cmax of imipramine and decreased clearance twofold. The effects on desipramine pharmacokinetics were even more pronounced. These findings indicate a significant interaction of paroxetine with the CYP2D6 isoenzyme.
MeSH terms
-
Adult
-
Antidepressive Agents, Tricyclic / blood
-
Antidepressive Agents, Tricyclic / metabolism*
-
Antidepressive Agents, Tricyclic / therapeutic use*
-
Cytochrome P-450 Enzyme System / metabolism
-
Depressive Disorder / blood
-
Depressive Disorder / drug therapy*
-
Depressive Disorder / psychology
-
Desipramine / metabolism
-
Drug Synergism
-
Humans
-
Imipramine / blood
-
Imipramine / metabolism*
-
Imipramine / therapeutic use*
-
Male
-
Middle Aged
-
Paroxetine / blood
-
Paroxetine / pharmacokinetics
-
Paroxetine / pharmacology*
-
Selective Serotonin Reuptake Inhibitors / pharmacology*
Substances
-
Antidepressive Agents, Tricyclic
-
Serotonin Uptake Inhibitors
-
Paroxetine
-
Cytochrome P-450 Enzyme System
-
Imipramine
-
Desipramine