TABLE 3

Comparison of parent and metabolite in vitro Ki values for literature cytochrome P450 inhibitors

Metabolite >4× More Potent than Parent (n = 6)Metabolite 1–4× More Potent than Parent (n = 13)Metabolite <1× Potent than Parent (n = 12)
Amiodarone (6.6×, desethyl, 2C9)Bupropion (4×, threo, 2D6)Amodiaquine (0.5×, desethyl, 2D6)
Bupropion (12×, erythro, 2D6)Bupropion (1.6×, hydroxy, 2D6)Clomipramine (0.5×, N-desmethyl, 2D6)
Atorvastatin (100×, lactone, 3A)Sulfinpyrazone (3×, sulfone, 2C9)Risperidone (0.4×, hydroxy, 2D6)
Citalopram (11×, didesmethyl, 2C19)Venlafaxine (1.5×, N-desmethyl, 2D6)Risperidone (0.8×, hydroxy, 3A)
Sulfinpyrazone (8×, sulfide, 2C9)Sertraline (1.4×, N-desmethyl, 2D6)Itraconazole (0.3×, hydroxy, 3A4)
Propranolol (4.5×, 4-hydroxy, 2D6)Sertraline (1×, N-desmethyl, 3A4)Ranolazine (0.9×, O-demethyl, 3A4)
Haloperidol (4×, reduced, 2D6)Imatinib (0.6×, N-desmethyl, 3A4)
Fluoxetine (1×, N-desmethyl, 2D6)Imatinib (0.6×, N-desmethyl, 2D6)
Citalopram (1.6×, desmethyl, 2C19)Carbamazepine (0.6×, epoxide, 2C19)
Chloroquine (1×, monodesethyl, 2D6)Omeprazole (0.2×, sulfone, 2C19)
Imatinib (1.5×, N-desmethyl, 2C9)Quinidine (0.01×, hydroxy, 2D6)
Atomoxetine (2×, N-desmethyl, 3A)Quinidine (0.001×, N-oxide, 2D6)
Omeprazole (1×, sulfone, 3A)
  • P, parent; M, metabolite; (fold change potency, metabolite structure, cytochrome P450).