Effect of venlafaxine on imipramine metabolism

Psychiatry Res. 2000 Nov 20;96(3):235-43. doi: 10.1016/s0165-1781(00)00213-4.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Antidepressive Agents, Tricyclic / blood
  • Antidepressive Agents, Tricyclic / pharmacokinetics*
  • Cross-Over Studies
  • Cyclohexanols / blood
  • Cyclohexanols / pharmacology*
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Desipramine / pharmacokinetics
  • Drug Interactions
  • Humans
  • Imipramine / blood
  • Imipramine / pharmacokinetics*
  • Male
  • Middle Aged
  • Phenotype
  • Venlafaxine Hydrochloride


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Cyclohexanols
  • Venlafaxine Hydrochloride
  • Cytochrome P-450 CYP2D6
  • Imipramine
  • Desipramine