Pharmacokinetics and drug interactions of antidepressive agents

Tricyclic antidepressive agents(TCAs) are conventional antidepressant. Cytochrome P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. The elimination of TCAs is impaired by CYP2D6 inhibitors such as quinidine. Newer antidepressants, selective serotonin uptake inhibitors(SSRIs), are also metabolized in the liver. Fluvoxamine, an SSRI, is a potent inhibitors for CYP1A2 and CYP2C19, moderate for CYP3A4 and weak for CYP 2D6. Paroxetine, another SSRI, causes substantial inhibition of CYP2D6 activity. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, is mainly excreted unchanged in urine and some part as its glucronide conjugate. In contrast to many SSRIs, milnacipran is devoid of metabolic inhibition.