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.
aPfizer Inc., formerly Wyeth Research, Collegeville, Pennsylvania
bDepartment of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA
Madelyn Abell, Jessica A. Behrle, Glen Frick and Jeffrey Paul are former employees of Wyeth Research.
Correspondence to Alice I. Nichols, PhD, Pfizer Inc., formerly Wyeth Research, 500 Arcola Rd, Collegeville, Pennsylvania 19426, USA Tel: +1 484 865 8741; fax: +1 484 865 9075; e-mail: email@example.com
Received January 25, 2012
Accepted October 31, 2012