Human liver P450s (CYPs), and some of the drugs metabolized (substrates), inducers, and selective inhibitors

Question 1

CYP1A2 (ProCarcinogenic)

Answer 1

Substrates: Acetaminophen, alosetron, antipyrine, caffeine, clomipramine, clozapine, duloxetine, flutamide, frovatriptan, melatonin, mexiletine, mirtazapine, olanzapine, phenacetin,
ramelteon, rasagiline, ropinirole, tacrine, tamoxifen, theophylline, tizanidine, triamterene, warfarin, zolmitriptan

Inducers: Charcoal-broiled foods,
cruciferous vegetables,
grilled meat, lansoprazole,
omeprazole, primidone,
rifampin, smoking

Inhibitors: Artemisinin, atazanavir, cimetidine, ciprofloxacin, enoxacin, Ethinyl estradiol, fluvoxamine, furafylline, galangin, mexiletene, tacrine, thiabendazole, zileuton

Question 2

CYP2A6

Answer 2

Substrates: Coumarin, dexmedetomidine, tobacco nitrosamines, nicotine
(to cotinine and 2′-hydroxynicotine)

Inducers: Efavirenz, rifampin,
phenobarbital

Inhibitors: Clotrimazole, isoniazid, ketoconazole, letrozole, menthofuran, methimazole, methoxsalen, miconazole,
tranylcypromine

Question 3

CYP2B6

Answer 3

Substrate: Artemisinin, bupropion, clopidogrel, cyclophosphamide,
efavirenz, ifosfamide, irinotecan, ketamine, S-mephobarbital,
S-mephenytoin (N-demethylation to nirvanol), methadone, nevirapine, promethazine, propofol, selegiline, sertraline, ticlopidine

Inducer: Carbamazepine, cyclophosphamide, fosphenytoin,
nevirapine, phenobarbital,
primidone, rifampin

Inhibitors: Amiodarone, amlodipine, clopidogrel, clotrimazole, desipramine, disulfiram, doxorubicin, ethinyl estradiol, fluoxetine, fluvoxamine, isoflurane, ketoconazole, mestranol, methimazole, nefazodone, nelfinavir, orphenadrine, paroxetine, phencyclidine, sertraline, thiotepa, ticlopidine

Question 4

CYP2C8

Answer 4

Substrate: Amiodarone, cabazitaxel, carbamazepine, chloroquine,
diclofenac, ibuprofen, paclitaxel, all-trans-retinoic acid, repaglinide, rosiglitazone, treprostinil

Inducer: Rifampin, barbiturates

Inhibitor: Deferasirox, gemfibrozil, lapatinib, montelukast, pioglitazone, quercetin, rosiglitazone, trimethoprim

Question 5

CYP2C9

Answer 5

Substrate: Alosetron, bosentan, celecoxib, chlorpropamide, diclofenac,
dronabinol, flurbiprofen, fluvastatin, glimepiride, glipizide,
glyburide, hexobarbital, ibuprofen, indomethacin, irbesartan,
losartan, meloxicam, montelukast, naproxen, nateglinide,
phenobarbital, phenytoin, piroxicam, rosiglitazone,
rosuvastatin, sulfamethoxazole, sulfaphenazole, ticrynafen,
tolbutamide, torsemide, trimethadione, valsartan, S-warfarin

Inducer: Aminoglutethimide,
barbiturates, bosentan,
carbamazepine, phenytoin,
primidone, rifabutin,
rifampin, rifapentine,
St. John’s wort

Inhibitor: Amiodarone, clopidogrel, delavirdine,
disulfiram, doxifluridine, efavirenz,
fluconazole, fluvoxamine, fluorouracil,
imatinib, leflunomide, metronidazole,
miconazole, phenytoin, sulfamethoxazole, sulfaphenazole, sulfinpyrazone,
tienilic acid, valproic acid, voriconazole

Question 6

CYP2C18

Answer 6

Substrate: Tolbutamide, phenytoin

Inducer: Phenobarbital

Inhibitor:

Question 7

CYP2C19

Answer 7

Substrate: Aripiprazole, carisoprodol, citalopram, clomipramine, clopidogrel, clozapine, desipramine, diazepam, diphenhydramine,
doxepin, escitalopram, fluoxetine, imipramine, lansoprazole,
S-mephenytoin, methadone, moclobemide, naproxen,
nelfinavir, nirvanol, olanzapine, omeprazole, pantoprazole,
phenobarbital, phenytoin, proguanil, propranolol, rabeprazole,
sertraline, thalidomide, voriconazole, R-warfarin

Inducer: Aminoglutethimide,
artemisinin, barbiturates,
carbamazepine, phenytoin,
primidone, rifampin,
rifapentine, St. John’s wort

inhibitor: N3-Benzylnirvanol, N3-benzylphenobarbital, chloramphenicol, cimetidine,
clopidogrel, delavirdine, efavirenz,
esomeprazole, felbamate, fluconazole,
fluoxetine, fluvoxamine, isoniazid,
moclobemide, modafinil, nootkatone,
omeprazole, ticlopidine, voriconazole

Question 8

CYP2D6

Answer 8

Substrate: Amitriptyline, atomoxetine, bufuralol, bupranolol, carvedilol,
chlorpheniramine, chlorpromazine, clomipramine, clozapine,
codeine, debrisoquine, desipramine, dextromethorphan,
dihydrocodeine, encainide, flecainide, fluoxetine, fluvoxamine, guanoxan, haloperidol, hydrocodone, imipramine,
maprotiline, 4–methoxy-amphetamine, metoclopramide,
metoprolol, mexiletine, nebivolol, nortriptyline, oxycodone,
palonosetron, paroxetine, perhexiline, perphenazine, phenformin, propafenone, propoxyphene, propranolol, risperidone, selegiline (deprenyl), sparteine, tamoxifen,
thioridazine, timolol, tolterodine, tricyclic antidepressants,
tramadol, trazodone, venlafaxine

Inducer

Inhibitor: Bupropion, cinacalcet, chloroquine,
diphenhydramine, fluoxetine,
haloperidol, imatinib, paroxetine,
propafenone, propoxyphene, quinidine,
terbinafine, thioridazine

Question 9

CYP2E1

Answer 9

Substrate: Acetaminophen, chlorzoxazone, dacarbazine, enflurane,
ethanol (a minor pathway), halothane, isoflurane, isoniazid,
sevoflurane, theophylline, trimethadione

Inducer: Ethanol, isoniazid

Inhibitor: Amitriptyline, chlorpromazine, cimetidine, clomethiazole, clotrimazole, clozapine, disulfiram, diethylthiocarbamate,
diallyl sulfide, econazole, methimazole,
methoxsalen, 4-methylpyrazole,
miconazole, modafinil, ritonavir,
selegiline, sildenafil, sulconazole,
ticlopidine, tioconazole

Question 10

CYP3A4/5 most common

Answer 10

Substrate: Acetaminophen, alfentanil, alfuzosin, almotriptan, alprazolam,
amiodarone, amlodipine, aprepitant, astemizole, atazanavir,
atorvastatin, bepridil, bexarotene, bosentan, bromocriptine,
budesonide, buspirone, carbamazepine, cisapride, clarithromycin, clonazepam, clopidogrel, cocaine, colchicine, conivaptan, cortisol, cyclosporine, dapsone, darunavir, dasatinib,
delavirdine, dexamethasone, diazepam, dihydroergotamine,
dihydropyridines, diltiazem, disopyramide, doxorubicin,
droperidol, dutasteride, ebastine, efavirenz, eletriptan, eplerenone, ergotamine, erlotinib, erythromycin, estazolam, eszopiclone, ethinyl estradiol, ethosuximide, etoposide, everolimus,
exemestane, felodipine, fentanyl, finasteride, flurazepam,
fluticasone, fosamprenavir, galantamine, gefitinib, gestodene,
granisetron, halofantrine, ifosfamide, imatinib, indinavir,
irinotecan, isradipine, itraconazole, ixabepilone, lapatinib,
lidocaine, loperamide, lopinavir, loratadine, lovastatin, macrolides, maraviroc, mefloquine, methadone, methylprednisolone, miconazole, midazolam, mifepristone, modafinil,
nefazodone, nevirapine, nicardipine, nifedipine, nimodipine,
nisoldipine, paclitaxel, paricalcitol, pimozide, pioglitazone,
praziquantel, prednisolone, prednisone, progesterone, quetiapine, quinacrine, quinidine, quinine, ranolazine, rapamycin,
repaglinide, rifabutin, ritonavir, saquinavir, sibutramine,
sildenafil, simvastatin, sirolimus, solifenacin, spironolactone,
sufentanil, sulfamethoxazole, sunitinib, tacrolimus, tadalafil,
tamoxifen, tamsulosin, teniposide, terfenadine, testosterone, tetrahydrocannabinol, tiagabine, tinidazole, tipranavir,
tolvaptan, topiramate, triazolam, troleandomycin, vardenafil,
verapamil, vinblastine, vincristine, ziprasidone, zolpidem,
zonisamide, zopiclone

Inducers: Aminoglutethimide,
avasimibe, barbiturates,
carbamazepine, efavirenz,
glucocorticoids, nevirapine,
pioglitazone, phenytoin,
primidone, rifampin, rifapentine, St. John’s wort

Inhibitor: Amprenavir, azamulin, boceprevir,
clarithromycin, conivaptan, diltiazem,
erythromycin, fluconazole, grapefruit
juice (furanocoumarins), indinavir,
itraconazole, ketoconazole, lopinavir,
mibefradil, nefazodone, nelfinavir,
posaconazole, ritonavir, saquinavir,
telaprevir, telithromycin, troleandomycin,
verapamil, voriconazole