Clin Pharmacokinet
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Several chemically unrelated agents has been developed and introduced in the past decade, to supplement the earlier antidepressants. These include inhibitors of the reuptake of serotonin [the selective serotonin reuptake inhibitors (SSRI)] or noradrenaline (reboxetine) or both (milnacipran and venlafaxine), as well as drugs with distinct neurochemical profiles such as mirtazapine, nefazodone, moclobemide and tianeptine. Like the earlier drugs, these newer antidepressants are almost totally biotransformed before excretion, except for milnacipran whose clearance appears to be due equally to both urinary excretion and metabolism. ⋯ Data on the brain-to-blood partition of metabolites compared with their parent drug are available only in a few cases. They are still not known for the main metabolites of fluvoxamine, milnacipran, mirtazapine, moclobemide, nefazodone, paroxetine, reboxetine and venlafaxine, despite the fact that total blood concentrations do not always reflect the metabolite: parent drug ratio in brain. Thus, in most cases, we do not really know what part hepatic metabolism plays in the overall effect of the administered parent drug.