Equal contribution of pharmacogenetic phenotype and phenoconversion to functional CYP2D6 metabolizer status

Pharmacogenetics (PGx) of CYP2D6 is gaining more importance in routine clinical settings. CYP2D6 is susceptible to inhibition. Thus, including phenoconversion effects (PC) in result interpretation may maximize precision benefits of PGx. However, studies including the functional enzyme status (PC-informed PGx) are lacking.

We aimed to investigate how the CYP2D6 functional enzyme status affects serum concentrations of psychotropic drugs. Using clinical routine data allows an evaluation of the relevance of this information for patient care.

Two patient cohorts (total n=316) were investigated for the CYP2D6 functional enzyme status and the associations with serum concentrations of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone and quetiapine.

When including PC, we found an increase in rates of CYP2D6 intermediate and poor metabolizers, as well as a decrease in normal metabolizers. Moreover, we found associations between amitriptyline serum concentration with the PC-corrected activity score of CYP2D6, and risperidone concentration with CYP2D6 functional enzyme status, as well as between metabolite-to-parent ratio of venlafaxine and risperidone with CYP2D6 functional enzyme status.

The data show the relevance of PC-informed PGx in psychopharmacological treatment. PC should be included in PGx result interpretation, to start with a dose adequate to the respective CYP2D6 functional enzyme status, especially before initiating amitriptyline- or risperidone-treatment. Moreover, PGx and therapeutic drug monitoring should be used complementary but not alternatively.

Publication History

Article published online:
12 March 2024