Cytochrome P450 : substrates, inhibitors and inducers

Bulletin (April - June 1998 Vol.6 No.2)

Cytochrome P450 : substrates, inhibitors and inducers

ปัจจุบันมีความพยายามศึกษาและค้นคว้าเพื่อให้ทราบว่ายาชนิดใดถูกเปลี่ยนแปลง (metabolize) ที่ cytochrome P450 ชนิดใด (substrate) ยาชนิดใดเป็นตัวยับยั้ง (inhibitor) และชนิดใดเป็นตัวเหนี่ยวนำ (inducer) ซึ่งข้อมูลดังกล่าวจะช่วยให้ สามารถคาดการณ์ถึงผลที่ผู้ป่วยอาจจะได้รับจากยาที่มีความเกี่ยวเนื่องกับ cytochrome P450 ในการทำให้เกิดปฏิกริยาต่อกันของยา (drug metabolism interaction) ได้ โดยเฉพาะอย่างยิ่งยาตัวใหม่ๆ ตารางต่อไปนี้ แสดงถึง substrates, inhibitors และ inducers ของระบบเอ็นไซม์ cytochrome P450 ที่ทราบในปัจจุบัน

Cytochrome P450		Substrates		Inhibitors	Inducers
CYP1A2	Acetaminophen, antipyrine, Caffeine, clomipramine, clozapine, Desipramine, Imipramine, Methadone, Nortriptyline, Ondansetron, Phenacetin, propranolol, Ritonavir, Tamoxifen, theophylline, Verapamil, Warfarin-(R)-isomer	Cimetidine, ciprofloxacin, Diltiazem, Erythromycin, Fluvoxamine, Mexiletine, Norfloxacin, Retonavir	Nicotine, Omeprazole, Phenobarbital, Rifampin, Tobacco smoke
CYP2A6	Ritonovir, Tamoxifen	Ritonavir	-
CYP2B6	Antipyrine, Cyclophosphamide, Ifosfamide, Tamoxifen	Orphenadrine	Phenobarbital, phenytoin, primidone
CYP2C8	Antipyrine, Benzphetamine, Diazepam, diclofenac, Omeprazole, Paclitaxel, Retinoic acid, Tolbutamide	Omeprazole	Phenobarbital, primidone
CYP2E1	Acetaminophen, acetone, aniline, Enflurane, Enflurane, ethanol, Halothane, Isoflurane,isoniazid, Ondansetron, Phenol, Ritonavir, Tamoxifen	Disulfiram, Ritonavir	Ethanol, Isoniazid
CYP2C18	Antipyrine, Naproxen, Omeprazole, Piroxicam, propranolol, Retinoic acid, THC-(s)-isomer, Warfarin-(R)-isomer	Cimetidine	-
CYP2C19	Clomipramine, Diazepam, Imipramine, Mephenytoin, Omeprazole, Propranolol, Ritonavir, Valproic acid	Fluoxetine, fluvoxamine, Omeprazole, Ritonavir, Tolbutamide	-
CYP2D6	Amitriptyline, Chlorpromazine,clomipramine, clozapine, codeine, Desipramine,dexfenfluramine , dextromethorphan, Fluoxetine, fluphenazine, Halofantrine, haloperidol, Imipramine, Labetalol, loratadine, Metoprolol, mexiletine, morphine, Nortriptyline, Ondansetron, Paroxetine, perphenazine, propranolol, Resperidone, ritonavir, Sertraline, Tamoxifen, thioridazine, timolol, tramadol, trazodone	Amiodarone, Cimetidine, codeine, Dextropropoxyphene, doxorubicin, Fluoxetine, fluphenazine, fluvoxamine, Haloperidol, Miberfradil, Paroxetine, perphenazine, Quinidine, Ranitidine, ritonavir, Sertraline, Thioridazine, Vinblastine	-
CYP2C9	Amitriptyline, antipyrine, Dapsone, diclofenac, Ibuprofen, imipramine, indomethacin, Mefenamic acid, Naproxen, Phenytoin, piroxicam, Ritonavir, Tolbutamide, Warfarin-(R)-isomer	Aminodarone, Diclofenac, disulfiram, Fluconazole, flurbiprofen, fluvastatin, fluvoxamine, Ketoprofen, Metronidazole, Phenylbutazone, Ritonavir, Sulfinpyrazone, sulfonamides, TMP/SMX	Rifampin
CYP3A4	Acetaminophen, alprazolam, amiodarone, amitriptyline, amlodipine, antipytine, astemizole, Bromocriptine, Carbamazepine, chlorpromazine, cisapride, clarithromycin, cocaine, codeine, cortisol, cyclophosphamide, cyclosporine, Dapsone, dextromethorphan, diazepam, diltiazem, Erythromycin, ethinyl estradiol, etoposide, Felodipine, fentanyl, Granisetron, Hydrocortisone, Ifosfamide, imipramine, indinavir, Lidocaine, loratadine, lovastatin, Miconazole, midazolam, Nevirapine, nicardipine, nifedipine, nitrendipine, Ondansetron, oral contraceptives, Paclitaxel, progesterone, propafenone, Quinidine, Ritonavir, Saquinavir, simvastatin, Tamoxifen, terfenadine, testosterone, tretinoin, triazolam, Venlafaxine, verapamil, vinblastine, vincristine	Cimetidine, clarithromycin, clotrimazole, Diltiazem, Erythromycin, Fluconazole, fluoxetine, fluoxamine, Grapefruit juice, Indinavir, itraconazole, Ketoconazole, Metronidazole, miberfradil, miconazole, Nelfinavir, Omeprazole, Paroxetine, Quinidine, Ranitidine, ritonavir Saquinavir	Carbamazepine, Dexamethasone, Glucocorticoids, Phenobarbital, phenylbutazone, phenytoin, primidone, Rifabutin, rifampin, Sulfinpyrazone
CYP3A5-7	Cortisol, Ethinyl estradiol, Lovastatin, Midazolam, Nifedepine, Quinidine, Terfenadine, testosterone, triazolam, Vinblastine, vincristine	Clotrimazole, Ketoconazole, Metronidazole, miconazole	Phenobarbital, phenytoin, primidone, Rifampin
UNKNOWN	Clotrimazole, Phenobarbital, primidone, Trimetrexate	Allopurinol, alpha-Interferon, Isoniazid, Propoxyphene, Ticlopidine, TMP/SMX, trimethoprim