Lack of pharmacokinetic interaction when switching from fluoxetine to milnacipran

International Clinical Psychopharmacology
Christian PuozzoDidier Chassard

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 administrat...Continue Reading

References

Mar 1, 1992·Clinical Pharmacology and Therapeutics·R F BergstromL Lemberger
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Oct 9, 2002·International Clinical Psychopharmacology·Christian PuozzoDominique Deprez

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Citations

Jul 22, 2009·Clinical Neuropharmacology·Chi-Un PaePrakash S Masand
Dec 17, 2011·CNS Drugs·Edoardo SpinaFilippo Caraci
Jul 18, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Brandy L ParisAndrew Parkinson
Feb 28, 2020·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova·N N Petrova, A V Markin
May 1, 2008·Bioorganic & Medicinal Chemistry Letters·Junko TamiyaChen Chen

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