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 therapeut ic profile that will allow them to be used in depressed patients who a re elderly or with cardiac, renal or hepatic disease. This article rev iews the pharmacokinetic characteristics of the tricyclic antidepressa nts, the selective serotonin reuptake inhibitors (SSRIs) and more rece ntly introduced antidepressants such as venlafaxine and nefazodone. Mi lnacipran (Ixel(R)), a novel drug, combines antidepressant efficacy wi th some unique pharmacokinetic features. A summary of its pharmacokine tic profile shows that milnacipran has a high bioavailability, low pla sma protein binding and that it is largely eliminated in the urine as parent drug or as a glucuronide. These features suggest that the likel ihood of interactions with other drugs given concurrently is lower tha n would occur with most second generation antidepressants and the tric yclic antidepressants. Furthermore, studies in patients with liver dys function, and in the elderly, suggest that dose adjustment is not nece ssary when milnacipran is administered to these patients. The decrease in milnacipran elimination is correlated to the degree of renal impai rment, allowing adjustment of schedules. In comparison to earlier anti depressants, milnacipran combines efficacy and a relatively low side-e ffect profile with the added advantage of fewer interactions with drug s that may be given concurrently.