norfluoxetine

Norfluoxetine is the N-desmethyl metabolite of fluoxetine (Prozac). It is produced in the liver by demethylation of fluoxetine and is pharmacologically active, contributing to the overall antidepressant effect of fluoxetine therapy. As a metabolite, norfluoxetine is present alongside fluoxetine in the body and can influence the duration of pharmacological activity after dosing.

Pharmacology wise, norfluoxetine functions as a selective serotonin reuptake inhibitor, inhibiting the serotonin transporter (SERT) and increasing serotonin availability in the synaptic cleft. Its activity is related to that of fluoxetine, with continued influence on serotonergic signaling even after the parent drug levels decline.

Pharmacokinetically, norfluoxetine has a longer elimination half-life than fluoxetine, which leads to its prolonged presence in systemic circulation. This extended persistence means that detectable levels of norfluoxetine can remain in the body for an extended period after fluoxetine administration ends, contributing to sustained pharmacologic effects and to the overall time course of drug exposure observed in pharmacokinetic studies.

Clinical considerations are primarily related to the combined effect of fluoxetine and its metabolites. The presence of norfluoxetine can influence the duration of action and the time to washout after discontinuation. Clinicians consider the metabolite when evaluating drug interactions and the potential for serotonergic effects, particularly in patients taking other serotonergic agents or with hepatic impairment that may affect metabolism.

Norfluoxetine is not marketed as an independent medication. It is not prescribed separately and is mainly discussed in the context of fluoxetine’s pharmacology, pharmacokinetics, and research analyses.