Pharmacokinetics of milnacipran in comparison with other antidepressants.
Despite the large number of antidepressants currently available, it is still necessary to develop new drugs that combine the efficacy of the older antidepressant with improved safety, tolerability and therapeutic profile that will allow them to be used in depressed patients who are elderly or with cardiac, renal or hepatic disease. This article reviews the pharmacokinetic characteristics of the tricyclic antidepressants, the selective serotonin reuptake inhibitors (SSRIs) and more recently introduced antidepressants such as venlafaxine and nefazodone. Milnacipran (Ixel), a novel drug, combines antidepressant efficacy with some unique pharmacokinetic features. A summary of its pharmacokinetic profile shows that milnacipran has a high bioavailability, low plasma protein binding and that it is largely eliminated in the urine as parent drug or as a glucuronide. These features suggest that the likelihood of interactions with other drugs given concurrently is lower than would occur with most second generation antidepressants and the tricyclic antidepressants. Furthermore, studies in patients with liver dysfunction, and in the elderly, suggest that dose adjustment is not necessary when milnacipran is administered to these patients. The decrease in milnacipran elimination is correlated to the degree of renal impairment, allowing adjustment of schedules. In comparison to earlier antidepressants, milnacipran combines efficacy and a relatively low side-effect profile with the added advantage of fewer interactions with drugs that may be given concurrently.
Puozzo
C
C
Institut de Recherche Pierre Fabre, Centre de Pharmacocinetique, Castres, France.
Leonard
B E
BE
D018759:Adrenergic Uptake Inhibitors / Q000493:pharmacokinetics*; D000367:Age Factors; D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics; D001682:Biological Availability; D003521:Cyclopropanes / Q000493:pharmacokinetics*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism; D008657:Metabolic Clearance Rate; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D003521:Cyclopropanes; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors