Paroxetine shifts imipramine metabolism.
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.
Albers
L J
LJ
Psychiatry Service, Long Beach Veterans Affairs Medical Center, CA 90822, USA.
Reist
C
C
Helmeste
D
D
Vu
R
R
Tang
S W
SW
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D003891:Desipramine / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007099:Imipramine / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000929:Antidepressive Agents, Tricyclic; D003577:Cytochrome P-450 Enzyme System; D003891:Desipramine; D007099:Imipramine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors