Which bioequivalence study for a racemic drug? Application to milnacipran

  title={Which bioequivalence study for a racemic drug? Application to milnacipran},
  author={Dominique Deprez and Didier Chassard and P. Baille and Alain Mignot and H. L. Ung and Christian Puozzo},
  journal={European Journal of Drug Metabolism and Pharmacokinetics},
SummaryMilnacipran, a new non tricyclic antidepressant drug, is a racemic mixture (F2207) composed of two enantiomers: F2695 and F2696, both demonstrated to be active. A randomized open label, single-dose latin square study was undertaken in 24 healthy volunteers to compare, based on racemate data, the relative bioavailability of two new formulations to that of a reference formulation. Later on, as suggested by actual regulatory trend, analysis was carried out on enantiomer data, although in a… 
Pharmacokinetics of milnacipran in renal impairment
The pharmacokinetics of milnacipran were markedly affected by impaired renal function with the elimination half-life of severly impaired subject being approximately three times that of the control group.
About the Misleading Use of Stereodescriptors in Labeling the Stereoisomers of Milnacipran and Levomilnacipran.
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  • Medicine
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The eutomer levomilnacipran HCl (code F2695) was commercialized in the United States under the trade name Fetzima as an antidepressant, rather than for the treatment of fibromyalgia.
Disposition and metabolism of [14C]-levomilnacipran, a serotonin and norepinephrine reuptake inhibitor, in humans, monkeys, and rats
Mass balance results indicated that renal excretion was the major route of elimination with 58.4%, 35.5%, and 40.2% of total radioactivity being excreted as unchanged levomilnacipran in humans, monkeys, and rats, respectively.
Development of Validated Stability Indicating RP-HPLC Method for the Estimation of levo-Milnacipran Hydrochloride in Pure and Pharmaceutical Formulations
A simple, specific, accurate and stability indicating RP-HPLC method was developed and validated for the determination of levo-Milnacipran hydrochloride in pure and tablet dosage form. The
Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant – what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
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The efficacy and safety of levomilnacipran (extended‐release capsules) for the treatment of major depressive disorder (MDD) are described.


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Clinicians must check the dosages of any accompanying medications with which rifampicin may potentially interact, and monitoring of clinical response and blood drug concentrations is essential to adjust the drug dosage during rifampsicin therapy.
A comparison of the Two One-Sided Tests Procedure and the Power Approach for assessing the equivalence of average bioavailability
This Power Approach is compared to another statistical approach, the Two One-Sided Tests Procedure, which leads to the same conclusion as the approach proposed by Westlake (2), based on the usual (shortest) 1–2α confidence interval for the true average difference.
Clinical pharmacokinetics : concepts and applications
The Third Edition of Clinical Pharmacokinetics features considerations of both stereochemistry and the increasing number of polypeptide and protein drugs being developed; the range and number of
Determination of milnacipran (F2207) and its glucuroconjugate in plasma, blood and urine by high performance liquid chromatography with fluorescence detection
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Enantioselective determination of the two enantiomers of rnilnacipran (F2207) in plasma and urine by gas chromatography-mass spectrometry
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