CYP2

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2C19 2D6 2E1 2G1 2J2 2R1
2S1  


CYP isoenzymes
# = found in lung tissue
CYP2 10 subfamilies, 15 genes, 8 pseudogenes
(drug and steroid metabolism) - about 20% of liver CYP!
Isoenzyme Substrates Inducer Inhibitor Alleles Effects (alleles, interactions)
CYP2A6
(about 4% of liver CYP)
nicotine,
7-hydroxylates coumarins
? ? *1 .. *5 (and variants) *2 : inactive (1-3% of Caucasians)
*4 : inactive
*5 : inactive (deletions common in Asians)
CYP2A13 (found in nasal mucosa) ? ? ? ?
CYP2B6 # artemisinin, S-mephobarbital, S-ifosfamide cyclophosphamide coumarin activation! phenobarbital, cyclophosphamide ? ? {used in retroviral vector gene Rx of cancer!}
expression in early childhood is poor
CYP2C8 # TCA, diazepam (found in kidney, adrenal, brain, uterus, breast, ovary & duodenum), verapamil rifampicin, phenobarbitone {despite lacking a 'Barbie box' : J Biochem Mol Toxicol 1999;13(6):289-95 } cimetidine -?-
expression in early childhood is poor
CYP2C9 S-warfarin, phenytoin, diclofenac & other NSAIDS, tolbutamide, fluoxetine, torsemide, verapamil , dextromethorphan

losartan (activated)
rifampicin, ? carbamazepine, ? ethanol fluconazole, ketoconazole, sulphonamides (sulfaphenazole), sulphinpyrazone, amiodarone, ritonavir, metronidazole
{cimetidine has a minimal effect}
*1 .. *3 *2, *3 : less active. phenytoin toxicity
CYP2C18 # (found in brain, uterus, breast, kidney & duodenum; liver levels ~10% of those of 2C8 and 2C9) Similar to 2C19; metabolises cyclophosphamide, ifosfamide , verapamil , lansoprazole
Isoenzyme Substrates Inducer Inhibitor Alleles Effects
CYP2C19 (found in duodenum but few other extrahepatic tissues; lower hepatic expression than 2C9) (S) mephenytoin, phenytoin, diazepam, TCA (clomipramine, imipramine..), dextromethorphan, propranolol, omeprazole, progesterone, sertraline, aminopyrine



meprobamate formation from carisoprodol, proguanil ? (activated)
phenobarbitone, artemisinin (?) sulfaphenazole, fluoxetine, omeprazole, ritonavir, fluvoxamine, oral contraceptives ticlopidine *1, *2 .. *8 *2 .. *8 : inactive (in up to 20% of Asians {*2 and *3}, 3% of Caucasians, 19% of African Americans, 8% of Africans, up to 71% of Pacific islanders ) Low activity allows dual Rx of H pylori with good success! Low B12 with long term omeprazole Rx!
risk of phenytoin toxicity (?)
CYP2D6
"debrisoquine hydroxylase" (about 2% of liver CYP, the only active 2D in man {rats have ~six!} ) found mainly in the liver, with LITTLE intestinal activity
debrisoquine, dextromethorphan, beta blockers,
haloperidol, chlorpromazine, thioridazine
dexfenfluramine,
flecainide, propafenone, mexiletine, procainamide
fentanyl, pethidine {=meperidine},
SSRIs (fluoxetine), TCAs, trazadone, zuclopenthixol, S-mianserin, tolterodine; azelastine ,

tramadol, codeine, venlafaxine, oxycodone (prodrug activation)
NOT INDUCIBLE;
(? does activity increase in pregnancy)
cimetidine { >>> ranitidine },
quini[di]ne, methadone, SSRIs,
some TCAs (paroxetine > fluoxetine = norfluoxetine > sertraline = desmethylsertraline > fluvoxamine, nefazodone, venlafaxine > clomipramine > amitriptyline),
antipsychotics (perphenazine > thioridazine > chlorpromazine > haloperidol > fluphenazine > risperidone > clozapine > cis-thiothixine )
dextropropoxyphene {?}, terbinafine
*1A .. *1E, *1XN, *2A, *2B .. *2K, *2XN, *3 .. *8, *9, *10, *11 .. *16, *17, *18, *19, *20, *21 .. *32, *33, *34, *35, *35X2, *36, *37, *38.
*10 (common in Chinese);
*17 (common in Black Africans);
~10% of Caucasians are poor metabolisers;
X = multiple copies (Ethiopian);

[ increased activity, normal activity, decreased activity, no activity, others unknown ]
Extensive metabolisers may get procainamide-induced SLE;

Isoenzyme Substrates Inducer Inhibitor Alleles Effects
CYP2E1 #
(about 7% of liver CYP)
paracetamol {=acetaminophen},
Many volatile anaesthetics: isoflurane, sevoflurane, enflurane, ..
ethanol
pentobarbitone, tolbutamide, propranolol, rifampicin

coumarin activation!

chronic ethanol intake, isoniazid, benzene disulfiram, (cimetidine) (acute ethanol intake!) *1A .. 1C, *1D, *2, *3, *4, *5 .. *7 *1D : (increased),
*2 : decreased
? association with alcoholic liver disease, liver cancer, lung & nasopharyngeal cancer (cigarettes) (Chinese polymorphism)

Noteworthy drug interactions

CYP2G1
(olfactory epithelium)
a steroid hydroxylase ? ? ? {may mediate olfactory toxicity of 2,6 dichlorobenzonitrile, and acetaminophen, at least in mice}
CYP2J2 Probably catalyses formation of epoxyeicosatrienoic acids (EETs), which modulate bronchial and vascular tone, ion transport and peptide hormone secretion! Found in gut (epithelial, endothelial, smooth muscle and autonomic ganglion cells), and widespread in human lung
CYP2R1 ?
CYP2S1 ?

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Last update 2000-1-22 Author jo@anaesthetist.com