Phase I enzymes
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CYP2C9 | tolbutamide, warfarin, phenytoin, non-steroidal anti-inflammatories | Anticoagulant effect of warfarin | (76–79) |
CYP2C19 | mephenytoin, omeprazole, hexobarbital, mephobarbital, propranolol, proguanil, phenytoin | peptic ulcer response to omeprazole | (80–81) |
CYP2D6 | β blockers, antidepressants, antipsychotics, codeine, debrisoquin, dextromethorphan, encainide, flecainide, fluoxetine, guanoxan, methoxy-amphetamine, N-propylajmaline, perhexiline, phenacetin, phenformin, propafenone, sparteine | tardive dyskinesia from antipsychotics, narcotic side effects, efficacy, and dependence, imipramine dose requirement, β blocker effect | (31,32,36,82–93) |
CYP3A4/3A5/3A7 | macrolides, cyclosporin, tacrolimus, calcium channel blockers, midazolam, terfenadine, lidocaine, dapsone, quinidine, triazolam, etoposide, teniposide, lovastatin, alfentanil, tamoxifen, steroids, benzo(a)pyrene | not yet elucidated, polymorphic 3A5 expression linked to 3A5 promoter polymorphism | (94–97) |
Dihydropyrimidine dehydrogenase | Fluorouracil | 5-fluorouracil neurotoxicity | (98–99) |
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Phase II enzymes
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N-acetyltransferase (NAT2) | isoniazid, hydralazine, sulfonamides, amonafide, procainamide, dapsone, caffeine | hypersensitivity to sulfonamides, amonafide toxicity, hydralazine induced lupus, isoniazid neurotoxicity | (100–105) |
Glutathione transferases GSTM1, M3, T1 | Several anticancer agents | Decreased response in breast cancer; more toxicity and worse response in AML | (48–50) |
Thiopurine methyltransferase UDP-glucuronosyl-transferase UGT1A1 | Mercaptopurine, thioguanine, azathioprine Irinotecan, bilirubin | Thiopurine toxicity and efficacy, risk of second cancers Irinotecan glucuronidation | (8, 17, 18, 28, 106–115) |
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Transporters
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MDR-1 | Natural product anticancer drugs, HIV protease inhibitors, digoxin | Decrease CD4 response in HIV infected patients, decreased digoxin AUC | (59, 64) |