Fluoxetine metabolism and pharmacological interactions: The role of cytochrome P450

A review with 103 references. Fluoxetine is the parent drug of the SSRI (selective serotonin reuptake inhibitor) antidepressant class, and is still one of the most highly used drugs of this class world-wide. Fluoxetine now has largely (albeit not completely) substituted older and less safe drugs such as tricyclic antidepressants. Different cytochrome P450 isoforms are involved in the metabolism of fluoxetine, however, the main active metabolite, norfluoxetine, is produced by the CYP2D6 action in the human liver. In this paper, the main metabolic characteristics of fluoxetine will be reviewed, with particular attention paid to the role of cytochrome isozymes. The pharmacological interactions of the drug will be overviewed, especially those concerning other drugs used in psychiatric clinics, such as antipsychotics and antidepressants and the relationships between pharmacological interactions and cytochrome activity will be discussed. Recently, much attention has been drawn to the therapeutic drug monitoring (TDM) of fluoxetine, and in particular to the analysis of fluoxetine enantiomers for which enantiomeric separations and enantioselective metabolism will also briefly be mentioned.