3 results on '"Puozzo, C."'
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2. Lack of pharmacokinetic interaction when switching from fluoxetine to milnacipran.
- Author
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Puozzo C, Hermann P, and Chassard D
- Subjects
- Adult, Area Under Curve, Cyclopropanes administration & dosage, Cyclopropanes blood, Cytochrome P-450 CYP2D6 metabolism, Drug Administration Schedule, Drug Interactions, Drug Therapy, Combination, Female, Fluoxetine administration & dosage, Fluoxetine analogs & derivatives, Fluoxetine blood, Half-Life, Humans, Male, Metabolic Clearance Rate, Methods, Milnacipran, Nausea chemically induced, Selective Serotonin Reuptake Inhibitors administration & dosage, Selective Serotonin Reuptake Inhibitors adverse effects, Selective Serotonin Reuptake Inhibitors pharmacokinetics, Time Factors, Vomiting chemically induced, Cyclopropanes pharmacokinetics, Fluoxetine pharmacokinetics
- 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.
- Published
- 2006
- Full Text
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3. Pharmacology and pharmacokinetics of milnacipran.
- Author
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Puozzo C, Panconi E, and Deprez D
- Subjects
- Adrenergic Uptake Inhibitors therapeutic use, Antidepressive Agents, Second-Generation therapeutic use, Cyclopropanes therapeutic use, Depressive Disorder drug therapy, Humans, Milnacipran, Receptors, Neurotransmitter drug effects, Selective Serotonin Reuptake Inhibitors therapeutic use, Adrenergic Uptake Inhibitors pharmacokinetics, Adrenergic Uptake Inhibitors pharmacology, Antidepressive Agents, Second-Generation pharmacokinetics, Antidepressive Agents, Second-Generation pharmacology, Cyclopropanes pharmacokinetics, Cyclopropanes pharmacology, Selective Serotonin Reuptake Inhibitors pharmacokinetics, Selective Serotonin Reuptake Inhibitors pharmacology
- Abstract
Milnacipran is a dual-action antidepressant drug with equivalent inhibitory action at noradrenaline and serotonin neuronal reuptake systems. This dual action has been demonstrated in vitro and in vivo in experimental animals, and ex vivo in man. Milnacipran has no relevant affinity for any neurotransmitter receptor studied, in particular postsynaptic adrenergic, muscarinic and histamine receptors, and is therefore expected to be devoid of the prominent side-effects of many earlier antidepressants. Studies in human volunteers have not demonstrated any impact of milnacipran on cognitive function, consistent with its lack of anticholinergic properties. These pharmacodynamic properties are well preserved in vivo in humans, because milnacipran is only metabolized to a limited extent, and therefore circulates in the body principally as the unchanged parent drug, which is the only pharmacologically active compound at clinical doses. The pharmacokinetic profile of milnacipran is characterized by rapid absorption, high bioavailability, low protein binding, and rapid elimination, both by hepatic glucuronidation and renal excretion. This gives milnacipran certain pharmacokinetic advantages, such as low inter-individual variation in plasma levels, low potential for drug interactions, and limited impact on hepatic cytochrome P450 systems. These pharmacokinetic properties differentiate milnacipran from most other antidepressant drugs and contribute to the good safety profile of milnacipran and allow it to be used simply and flexibly in clinical practice.
- Published
- 2002
- Full Text
- View/download PDF
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