Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development.

Article Details

Citation

Zhou SF, Zhou ZW, Yang LP, Cai JP

Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development.

Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1.

PubMed ID
19515014 [ View in PubMed
]
Abstract

Cytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin). Some natural and herbal compounds are also metabolized by CYP2C9, probably leading to the formation of toxic metabolites. CYP2C9 also plays a role in the metabolism of several endogenous compounds such as steroids, melatonin, retinoids and arachidonic acid. Many CYP2C9 substrates are weak acids, but CYP2C9 also has the capacity to metabolise neutral, highly lipophilic compounds. A number of ligand-based and homology models of CYP2C9 have been reported and this has provided insights into the binding of ligands to the active site of CYP2C9. Data from the site-directed mutagenesis studies have revealed that a number of residues (e.g. Arg97, Phe110, Val113, Phe114, Arg144, Ser286, Asn289, Asp293 and Phe476) play an important role in ligand binding and determination of substrate specificity. The resolved crystal structures of CYP2C9 have confirmed the importance of these residues in substrate recognition and ligand orientation. CYP2C9 is activated by dapsone and its analogues and R-lansoprazole in a stereo-specific and substrate-dependent manner, probably through binding to the active site and inducing positive cooperativity. CYP2C9 is subject to induction by rifampin, phenobarbital, and dexamethasone, indicating the involvement of pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor in the regulation of CYP2C9. A number of compounds have been found to inhibit CYP2C9 and this may provide an explanation for some clinically important drug interactions. Tienilic acid, suprofen and silybin are mechanism-based inhibitors of CYP2C9. Given the critical role of CYP2C9 in drug metabolism and the presence of polymorphisms, it is important to identify drug candidates as potential substrates, inducer or inhibitors of CYP2C9 in drug development and drug discovery scientists should develop drugs with minimal interactions with this enzyme. Further studies are warranted to explore the molecular determinants for ligand-CYP2C9 binding and the structure-activity relationships.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
AcenocoumarolVitamin K epoxide reductase complex subunit 1ProteinHumans
Yes
Inhibitor
Details
TrabectedinDNANucleotideHumans
Yes
Binder
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
AceclofenacCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
AcenocoumarolCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
AcenocoumarolCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
AlprazolamCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
AlprazolamCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 2C18ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
AminophenazoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
AmiodaroneCytochrome P450 2C8ProteinHumans
Yes
Substrate
Details
AmiodaroneCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Details
AmiodaroneCytochrome P450 2D6ProteinHumans
Unknown
Inhibitor
Details
AmiodaroneCytochrome P450 3A4ProteinHumans
Yes
Substrate
Inhibitor
Details
AmprenavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
AntipyrineCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
AntipyrineCytochrome P450 2C18ProteinHumans
Unknown
Substrate
Details
AntipyrineCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
AntipyrineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
AntipyrineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
AtazanavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
AtorvastatinCytochrome P450 2B6ProteinHumans
No
Inducer
Details
AtorvastatinCytochrome P450 3A4ProteinHumans
No
Substrate
Details
BortezomibCytochrome P450 2C19ProteinHumans
No
Substrate
Inhibitor
Details
BortezomibCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
BosentanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inducer
Details
BosentanCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
BuprenorphineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
BuprenorphineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
BuprenorphineCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Details
BuprenorphineCytochrome P450 3A7ProteinHumans
Unknown
Substrate
Details
CaffeineCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Inhibitor
Details
CaffeineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
CandesartanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
CandesartanProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
CandesartanUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
Candesartan cilexetilProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
Candesartan cilexetilUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
CarvedilolCytochrome P450 1A1ProteinHumans
Unknown
Substrate
Details
CarvedilolCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
CelecoxibCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
CerivastatinCytochrome P450 2B6ProteinHumans
Unknown
Inducer
Details
CerivastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CerivastatinCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
ChlorpropamideCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
ChlorpropamideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
ChlorpropamideProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 1A1ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
CinnarizineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
CitalopramCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
CitalopramCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
ClopidogrelCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
ClozapineDimethylaniline monooxygenase [N-oxide-forming] 3ProteinHumans
Unknown
Substrate
Details
ClozapineUDP-glucuronosyltransferase 1-4ProteinHumans
Unknown
Substrate
Details
DapsoneArylamine N-acetyltransferase 2ProteinHumans
Unknown
Substrate
Details
DapsoneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
DapsoneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inducer
Details
DapsoneDimethylaniline monooxygenase [N-oxide-forming] 3ProteinHumans
Unknown
Substrate
Details
DapsoneMyeloperoxidaseProteinHumans
Unknown
Substrate
Details
DapsoneProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
DapsoneProstaglandin G/H synthase 2ProteinHumans
Unknown
Substrate
Details
DelavirdineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
DexibuprofenCytochrome P450 2C9ProteinHumans
No
Substrate
Details
DexibuprofenUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Details
DexibuprofenUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
DexibuprofenUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
DexibuprofenUDP-glucuronosyltransferase 2B4ProteinHumans
Unknown
Substrate
Details
DexibuprofenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
DextromethorphanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
DiazepamCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
DiazepamCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
DiazepamCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
DiazepamProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
DiclofenacUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
DiphenhydramineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
DiphenhydramineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
DiphenhydramineProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
DonepezilCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
DonepezilCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
DonepezilCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
DronabinolCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
DronabinolCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
DronabinolProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
EfavirenzCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inducer
Details
EletriptanCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
EletriptanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
EletriptanCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
EletriptanProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
EszopicloneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
EszopicloneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
EtodolacUDP-glucuronosyltransferase 1-10ProteinHumans
Unknown
Substrate
Details
EtodolacUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
EtodolacUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
EtodolacUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
EtoricoxibCytochrome P450 2D6ProteinHumans
Unknown
Inhibitor
Details
EtoricoxibCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
FlunarizineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
FlunarizineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
FlurbiprofenUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Inhibitor
Details
FlurbiprofenUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
FlurbiprofenUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
FlurbiprofenUDP-glucuronosyltransferase 2B4ProteinHumans
Unknown
Substrate
Details
FlurbiprofenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
FluvastatinCytochrome P450 1A1ProteinHumans
Unknown
Substrate
Inducer
Details
FluvastatinCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details
FluvastatinCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
FluvoxamineCytochrome P450 2C9ProteinHumans
No
Inhibitor
Details
FosphenytoinCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inducer
Details
GavestinelUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Details
GavestinelUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
GavestinelUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
GavestinelUDP-glucuronosyltransferase 2B4ProteinHumans
Unknown
Substrate
Details
GliclazideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
GlimepirideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
GlipizideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
GlyburideCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
GlyburideCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
HaloperidolCarbonyl reductase [NADPH] 1ProteinHumans
Unknown
Substrate
Details
HaloperidolUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
HexobarbitalCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
HexobarbitalCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
HexobarbitalProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
IbuprofenUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
IbuprofenUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
IbuprofenUDP-glucuronosyltransferase 2B4ProteinHumans
Unknown
Substrate
Details
IbuprofenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
IfosfamideCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
IfosfamideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
IfosfamideCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
IfosfamideCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Details
IfosfamideProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
ImatinibCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImatinibCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Inhibitor
Details
ImatinibProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
IndinavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
IndomethacinCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
IndomethacinCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
IndomethacinLiver carboxylesterase 1ProteinHumans
Unknown
Substrate
Details
IndomethacinUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Inhibitor
Details
IrbesartanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
IrbesartanProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
IrbesartanUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
KetamineProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
KetobemidoneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
KetobemidoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
KetobemidoneProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
KetobemidoneUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
KetoprofenCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
LansoprazoleCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Inducer
Details
LeflunomideCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
LicofeloneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details
LicofeloneCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
LicofeloneCytochrome P450 2J2ProteinHumans
Unknown
Substrate
Details
LicofeloneUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
LosartanCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
LosartanCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
LosartanUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Details
LosartanUDP-glucuronosyltransferase 1-10ProteinHumans
Unknown
Substrate
Details
LosartanUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
LosartanUDP-glucuronosyltransferase 2B17ProteinHumans
Unknown
Substrate
Details
LosartanUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
LumiracoxibCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
LumiracoxibCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
LumiracoxibUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
MephenytoinCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
MephenytoinCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
MephenytoinCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
MestranolCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
MitiglinideUDP-glucuronosyltransferase 1-3ProteinHumans
Unknown
Substrate
Details
MitiglinideUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
MontelukastCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
MontelukastCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
MontelukastProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
NaproxenCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
NaproxenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
NateglinideCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
NateglinideProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
NateglinideUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
NelfinavirCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inducer
Details
NelfinavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
NevirapineCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
NevirapineCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Inducer
Details
NevirapineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
NevirapineCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Details
NortriptylineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
NortriptylineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Inhibitor
Details
OmeprazoleCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
OmeprazoleCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
ParoxetineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
ParoxetineCytochrome P450 2C9ProteinHumans
Unknown
Inhibitor
Details
PhenobarbitalCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inducer
Details
PhenobarbitalCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inducer
Details
PhenprocoumonCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
PioglitazoneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Inhibitor
Details
PioglitazoneCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
PromazineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
PromazineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
PropofolUDP-glucuronosyltransferase 1-8ProteinHumans
Unknown
Substrate
Details
PropofolUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
RepaglinideCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
RifampicinCytochrome P450 2C9ProteinHumans
Unknown
Inducer
Details
RofecoxibCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Inhibitor
Details
RofecoxibCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
RofecoxibProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
RosiglitazoneProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
Salicylic acidCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
SaquinavirCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inhibitor
Details
SeratrodastCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
SeratrodastCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
SeratrodastCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
SeratrodastCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
SeratrodastProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
SeratrodastUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
SildenafilCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
SildenafilCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
SildenafilCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
SimvastatinCytochrome P450 2B6ProteinHumans
Unknown
Inhibitor
Inducer
Details
SimvastatinCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
SulfamethoxazoleArylamine N-acetyltransferase 1ProteinHumans
Unknown
Substrate
Details
SulfamethoxazoleArylamine N-acetyltransferase 2ProteinHumans
Unknown
Substrate
Details
SuprofenUDP-glucuronosyltransferase 1-1ProteinHumans
Unknown
Substrate
Details
SuprofenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
TerbinafineCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
TerbinafineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
TerbinafineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Inducer
Details
TerbinafineProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
ThalidomideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
ThalidomideCytochrome P450 3A5ProteinHumans
No
Inducer
Details
ThalidomideProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
ThalidomideProstaglandin G/H synthase 2ProteinHumans
Unknown
Substrate
Details
TiclopidineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Inhibitor
Details
TiclopidineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Inhibitor
Details
TiclopidineMyeloperoxidaseProteinHumans
Unknown
Substrate
Details
TolbutamideCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
TolbutamideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
TolterodineCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
TolterodineCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
TolterodineCytochrome P450 2D6ProteinHumans
Unknown
Substrate
Details
TorasemideCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
TrabectedinCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Details
TrabectedinProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
ValdecoxibCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
ValdecoxibUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
Valproic acidCytochrome P450 2A6ProteinHumans
Unknown
Substrate
Details
Valproic acidCytochrome P450 2B6ProteinHumans
Unknown
Substrate
Details
Valproic acidCytochrome P450 2C9ProteinHumans
Unknown
Substrate
Inhibitor
Details
Valproic acidCytochrome P450 3A5ProteinHumans
Unknown
Substrate
Details
Valproic acidProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
Valproic acidUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
VenlafaxineCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
VerapamilCytochrome P450 2C9ProteinHumans
Unknown
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Inhibitor
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VerapamilCytochrome P450 3A4ProteinHumans
Unknown
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VicrivirocCytochrome P450 2C9ProteinHumans
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VicrivirocCytochrome P450 3A4ProteinHumans
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VicrivirocCytochrome P450 3A5ProteinHumans
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VoriconazoleCytochrome P450 3A4ProteinHumans
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VoriconazoleDimethylaniline monooxygenase [N-oxide-forming] 3ProteinHumans
Unknown
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VoriconazoleProstaglandin G/H synthase 1ProteinHumans
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WarfarinCytochrome P450 1A2ProteinHumans
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WarfarinCytochrome P450 2C19ProteinHumans
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WarfarinCytochrome P450 2C8ProteinHumans
Unknown
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WarfarinCytochrome P450 3A4ProteinHumans
Unknown
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Inducer
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ZafirlukastCytochrome P450 2C9ProteinHumans
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ZafirlukastProstaglandin G/H synthase 1ProteinHumans
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ZaltoprofenCytochrome P450 2C9ProteinHumans
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ZaltoprofenProstaglandin G/H synthase 1ProteinHumans
Unknown
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ZaltoprofenUDP-glucuronosyltransferase 2B7ProteinHumans
Unknown
Substrate
Details
ZileutonCytochrome P450 1A2ProteinHumans
Unknown
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Inhibitor
Details
ZileutonCytochrome P450 3A4ProteinHumans
Unknown
Substrate
Details
ZileutonProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
ZileutonUDP-glucuronosyltransferase 1-9ProteinHumans
Unknown
Substrate
Details
ZolpidemCytochrome P450 2C19ProteinHumans
Unknown
Substrate
Details
ZopicloneCytochrome P450 2C8ProteinHumans
Unknown
Substrate
Details
ZopicloneProstaglandin G/H synthase 1ProteinHumans
Unknown
Substrate
Details
Drug Reactions
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Dapsone mercaptal intermediate
DBMET01045Thumb
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    Sulfamethoxazole N4-hydroxylamine
    DBMET00015Thumb
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      4-Hydroxycyclophosphamide
      DBMET00019Thumb
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        Voriconazole N-Oxide
        DBMET00071Thumb
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          Haloperidol 1,2,3,6-tetrahydropyridine
          DBMET00106Thumb
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            4'-Hydroxy-5-carboxylumiracoxib (M5)
            DBMET01285Thumb
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              Rofecoxib-erythro-3,4-dihydrohydroxy acid
              DBMET00172Thumb
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                Rofecoxib-threo-3,4-dihydrohydroxy acid
                DBMET00171Thumb
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                  Pioglitazone metabolite M-II
                  DBMET01301Thumb
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                    5-Methoxytryptamine
                    DBMET01359Thumb
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                        Drug Interactions
                        DrugsInteraction
                        Paroxetine
                        Cimetidine
                        The serum concentration of Paroxetine can be increased when it is combined with Cimetidine.
                        Interactions
                        Identify potential medication risks
                        Easily compare up to 40 drugs with our drug interaction checker.
                        Get severity rating, description, and management advice.
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