ArticleClinical pharmacokinetics2005
Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants.
Article in Clinical pharmacokinetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Milnacipran versus other antidepressive agents for depression.The Cochrane database of systematic reviews · 2009Pooled it
- Pooled it
- Single- and Multiple-Dose Milnacipran Pharmacokinetics in Healthy Han Chinese Volunteers.Clinical pharmacokinetics · 2016Trial
- Milnacipran and Vanillin Alleviate Fibromyalgia-Associated Depression in Reserpine-Induced Rat Model: Role of Wnt/β-Catenin Signaling.Molecular neurobiology · 2025Article
- Systemic and Brain Pharmacokinetics of Milnacipran in Mice: Comparison of Intraperitoneal and Intravenous Administration.Pharmaceutics · 2023Article
- Milnacipran for the Treatment of Fibromyalgia.Health psychology research · 2021Review
- Review
- Getting the balance right: Established and emerging therapies for major depressive disorders.Neuropsychiatric disease and treatment · 2010Article
- Milnacipran: a selective serotonin and norepinephrine dual reuptake inhibitor for the management of fibromyalgia.Therapeutic advances in musculoskeletal disease · 2010Article
- New and emerging therapeutic agents for the treatment of fibromyalgia: an update.Journal of pain research · 2010Article
- Role and rationale for the use of milnacipran in the management of fibromyalgia.Neuropsychiatric disease and treatment · 2010Article
- Milnacipran for the management of fibromyalgia syndrome.Journal of pain research · 2010Article
- Milnacipran: in fibromyalgia.Drugs · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo compare the pharmacokinetics of milnacipran in extensive metabolisers (EMs) and poor metabolisers (PMs) of sparteine and mephenytoin, and to assess the influence of multiple administrations of milnacipran on the activity of cytochrome P450 (CYP) isoenzymes through its own metabolism and through various probes, namely CYP2D6 (sparteine/dextromethorphan), CYP2C19 (mephenytoin), CYP1A2 (caffeine) and CYP3A4 (endogenous 6-beta-hydroxy-cortisol excretion).
methodsTwenty-five healthy subjects, 12 EMs for both sparteine/dextromethorphan and mephenytoin, nine EMs for mephenytoin and PMs for sparteine/dextromethorphan (PM(2D6)) and four PMs for mephenytoin and EMs for sparteine/dextromethorphan (PM(2C19)) were administered milnacipran as a single 50 mg capsule on day 1 followed by a 50 mg capsule twice daily for 7 days. The pharmacokinetics of milnacipran and its oxidative metabolites were assessed after the first dose (day 1) and after multiple administration (day 8), and were compared for differences between CYP2D6 and CYP2C19 PMs and EMs. Metabolic tests were performed before (day -2), during (days 1 and 8) and after (day 20) milnacipran administration.
resultsMilnacipran steady state was rapidly achieved. Metabolism was limited: approximately 50% unchanged drug, 30% as glucuronide and 20% as oxidative metabolite (mainly F2800 the N-dealkyl metabolite). Milnacipran administration to PM2D6 and PM2C19 subjects did not increase parent drug exposure or decrease metabolite exposure. Milnacipran oxidative metabolism is not mediated through CYP2D6 or CYP2C19 polymorphic pathways nor does it significantly interact with CYP1A2, CYP2C19, CYP2D6 or CYP3A4 activities.
conclusionLimited reciprocal pharmacokinetic interaction between milnacipran and CYP isoenzymes would confer flexibility in the therapeutic use of the drug when combined with antidepressants. Drug-drug interaction risk would be low, even if the combined treatments were likely to inhibit CYP2D6 and CYP2C19 isoenzyme activities.
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Registered trials
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