TABLE 5

Summary of estimated fraction metabolized by CYP2D6 in vitro and in vivo

Drug
fm CYP2D6a (Literature)
Metabolite Recoveryb (EM)
Estimated fm CYP2D6c
Estimated fm CYP2D6d (in Vitro)
Amitriptyline 0.83 0.50 0.42 0.53 ± 0.03
Atomoxetine >0.90 0.87 0.87 0.97 ± 0.04
Desipramine Majore 0.68 0.68 0.80 ± 0.08
Dextromethorphan Majore N.D.f 0.90 0.93 ± 0.04
Duloxetine Majore 0.50 0.50 0.87 ± 0.06
Imipramine 0.80 0.44 0.35 0.67 ± 0.03
Propafenone N.D. >0.70f 0.70 0.74 ± 0.03
Propranolol 0.40 0.42 0.17 0.76 ± 0.03
Sertraline <0.20-0.35 N.D.f 0.32 0.37 ± 0.04
Tolterodine Majore 0.70 0.70 0.79 ± 0.03
Venlafaxine
Majore
0.72
0.72
0.85 ± 0.07

  • N.D., not determined.

  • ↵ a Estimated conversion to specific metabolite(s) catalyzed by CYP2D6 in vitro.

  • ↵ b Metabolite(s) recovery in vivo for CYP2D6 products taken from Dorne et al. (2002).

  • ↵ c Calculated as the product of the fractional conversion by CYP2D6 taken from the literature and metabolite recovery in EM subjects.

  • ↵ d Fraction metabolized by CYP2D6 using microsomal incubations measuring substrate depletion with and without 1 μM quinidine.

  • ↵ e For drugs with a major contribution by CYP2D6 in vitro, a value of 1 was used for the calculation of estimated fraction metabolized by CYP2D6 in vivo.

  • ↵ f For drugs without metabolite recovery data reported in the literature, a value of 0.90 was used for the calculation of estimated fraction metabolized by CYP2D6 in vivo.