title: Effect of venlafaxine on imipramine metabolism.
abstract: The present study was designed to determine the effect of venlafaxine on imipramine metabolism in an attempt to elucidate the potential for cytochrome P450 drug-drug interactions with venlafaxine. We examined the metabolism of a single 100-mg dose of imipramine before and after treatment with venlafaxine, 50 mg three times a day. Eight male subjects were phenotyped for CYP2D6 activity. Two subjects were poor metabolizers of dextromethophan, and data from the remaining six subjects (mean age=45.3+/-15) were analyzed. Venlafaxine increased imipramine C(max) and elevated AUC by 40%. Desipramine clearance and volume of distribution were reduced by 20% and 25%, respectively. These findings are consistent with a statistically significant, but clinically modest impact of venlafaxine on CYP2D6-metabolized substrates.
authors.affiliation: Department of Psychiatry, University of California, California College of Medicine, Irvine, CA 92697, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Albers
authors.forename: C
authors.initials: C
authors.lastname: Reist
authors.forename: R L
authors.initials: RL
authors.lastname: Vu
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: V
authors.initials: V
authors.lastname: Ozdemir
authors.forename: D
authors.initials: D
authors.lastname: Helmeste
authors.forename: R
authors.initials: R
authors.lastname: Poland
authors.forename: S W
authors.initials: SW
authors.lastname: Tang
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003511:Cyclohexanols / Q000097:blood / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism*; D003891:Desipramine / Q000493:pharmacokinetics; D004347:Drug Interactions; D006801:Humans; D007099:Imipramine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6; D007099:Imipramine; D003891:Desipramine