Pharmacokinetics of fluoxetine and its effects on cytochrome P450 isoenzymes / 中国药理学通报

ABSTRACT

Fluoxetine is a relatively novel class of selective serotonin reuptake inhibitors (SSRIs) with antidepressant properties. It seems to facilitate serotonergic transmission via down regulation of presynaptic inhibitory autoreceptors, with no effect on muscarinic receptors and doubtful effects on ? adrenergic receptors. Fluoxetine is mainly metabolized by cytochrome P450 (CYP) isoenzymes. It has been shown that CYP2C9、CYPD6, and CYP2C19 are major CYP isoforms responsible for the N demethylation of fluoxetine. Since both fluoxetine and its main metabolite norfluoxetine are the inhibitors of CYP2D6, CYP3A4, CYP2C9, and CYP2C19, there are some drug drug interactions of fluoxetine with other drugs for metabolism by those CYP isoenzymes, which results in interindividual differences in the pharmacokinetics and efficacy.