Effect of venlafaxine on imipramine metabolism.
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.
Albers
L J
LJ
Department of Psychiatry, University of California, California College of Medicine, Irvine, CA 92697, USA.
Reist
C
C
Vu
R L
RL
Fujimoto
K
K
Ozdemir
V
V
Helmeste
D
D
Poland
R
R
Tang
S W
SW
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
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6; D007099:Imipramine; D003891:Desipramine