Figure 2. Phenoconversion of CYP2D6 in presence of strong (SI) or moderate (MI) inhibitors and metabolism of drugs by CYP2D6 phenotypes.

Figure 2a shows the phenoconversion in presence of SI and metabolism of active drug (green bars) to inactive metabolite (open bars) and prodrug (open bars) to active metabolite (green bars) in phenoconverted CYP2D6 phenotypic PMs(pPM). SI can decrease the activity of the CYP2D6 enzymes to null and phenoconvert the gUM, gNM or gIM to pPM. Thus, the pPM cannot metabolize the drug.

Figure 2b shows the phenoconversion in presence of MI and metabolism of active drug (green bars) to inactive metabolite (open bars) and prodrug (open bars) to active metabolite (green bars) in phenoconverted CYP2D6 phenotypic IMs(pIM). MI can decrease the activity of the CYP2D6 enzymes to nearly half and can phenoconvert the gUM, gNM or gIM to pIM. Thus, the pIM metabolizes the drug very slowly and to a lower extent (2 out of 6 units).

Note: For gUMs, in presence of three or more normal functioning alleles MI can phenoconvert them to NM or UM (not shown in the figure).

SI- strong inhibitors; MI- moderate inhibitor; gUM- genotypic ultrarapid metabolizer; gNM- genotypic normal metabolizer; gIM- genotypic intermediate metabolize; pPM- phenotypic PM; pIM- phenotypic IM; PM- poor metabolizer; IM- intermediate metabolizer.