Skip Navigation LinksHome > March 2013 - Volume 28 - Issue 2 > Effects of desvenlafaxine on the pharmacokinetics of desipra...
International Clinical Psychopharmacology:
doi: 10.1097/YIC.0b013e32835c1f49
Original Articles

Effects of desvenlafaxine on the pharmacokinetics of desipramine in healthy adults

Nichols, Alice I.a; Madelyn, Abella; Chen, Yangb; Behrle, Jessica A.a; Frick, Glena; Paul, Jeffreya

Collapse Box

Abstract

The results of two single-center, two-period, open-label trials that evaluated the effects of multiple doses of desvenlafaxine on the pharmacokinetics of desipramine, a cytochrome P450 (CYP) 2D6 enzyme substrate, are presented. Healthy individuals aged 18–45 years were administered a single oral dose of 50 mg desipramine with and without 100 mg daily (n=34) or 400 mg daily (n=23) desvenlafaxine for 5 days. After coadministration of 100 mg desvenlafaxine, desipramine exposure, measured by peak plasma concentration (C max) and total area under the plasma concentration-versus-time curve (AUC), showed minimal increases of 25 and 17%, respectively; coadministration of 400 mg desvenlafaxine resulted in a 52% increase in desipramine C max and a 90% increase in AUC. For the 100 mg dose, the geometric least squares mean ratios and 90% confidence intervals (CIs) for desipramine AUC (117%; 90% CI 110–125%), 2-hydroxydesipramine AUC (114%; 90% CI 110–119%), and C max (110%; 90% CI 104–116%) were all within the 80–125% interval, showing the bioequivalence for AUC between desipramine administered alone and in combination with 100 mg desvenlafaxine. These results indicate that desvenlafaxine is a relatively weak inhibitor of CYP2D6 and that desvenlafaxine 100 mg, twice the recommended therapeutic dose of 50 mg, is unlikely to cause drug–drug interactions with CYP2D6 substrates.

© 2013 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Share

Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.