ORIGINAL ARTICLESLack of pharmacokinetic interaction when switching from fluoxetine to milnacipranPuozzo, Christiana; Hermann, Philippea; Chassard, DidiercAuthor Information aClinical Pharmacokinetic Department, Institut de Recherche Pierre Fabre, Castres, France bSGS Biopharma SA, Wavre, Belgium cAster, Paris, France Correspondence and requests for reprints to Dr C. Puozzo, Clinical Pharmacokinetic Department, Institut de Recherche Pierre Fabre, 2 rue Christian d'Espic, 81106 Castres Cedex, France Tel: +33 5637 14637; e-mail: [email protected] Received 31 May 2005 Accepted 24 October 2005 International Clinical Psychopharmacology: May 2006 - Volume 21 - Issue 3 - p 153-158 doi: 10.1097/01.yic.0000188217.69537.dc Buy Metrics Abstract The lack of a therapeutic effect or unsupportable side-effects can lead to substitution of one antidepressant by another. The present study investigated potential modifications to the pharmacokinetic profile of milnacipran at steady-state when it is substituted for fluoxetine without any washout period. The open-label, multiple dose, three-period study was carried out in 12 evaluable healthy volunteers. A reference period (period 1) comprising a 3.5-day treatment with milnacipran at 50 mg b.i.d. was followed, after a 5–10-day washout, by 3 weeks of administration of 20 mg fluoxetine once daily (period 2), immediately followed by a further 3.5 days of administration of milnacipran at 50 mg b.i.d. (period 3). Blood samples collected at each period were analysed for milnacipran, N-dealkyl milnacipran, fluoxetine and norfluoxetine. Potential drug–drug interactions were evaluated by comparing milnacipran pharmacokinetic parameters between periods 1 and 3. A steady-state of fluoxetine and its metabolite was effectively reached by the end of the 3-week period. A steady-state of milnacipran was reached on day 2 of both periods 1 and 3. Trough concentrations of milnacipran were 66 and 65 ng/ml before and after the fluoxetine administration period, respectively. Cmax values were 226 and 248 ng/ml. When comparing the kinetic parameters of milnacipran before and after fluoxetine treatment, all the 90% confidence intervals were in the 20% range. No significant difference in the adverse events of milnacipran was observed before or after fluoxetine administration. © 2006 Lippincott Williams & Wilkins, Inc.