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WARFARIN PHARMACOKINETICS PATHWAY (PW:0000730)

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Description

Warfarin, trade name Coumadin, is a widely-used oral anticoagulant drug for the prevention of thrombosis and venous and arterial thromboembolism. It is a synthetic derivative of coumarin-derived dicoumarol. Warfarin is present as a racemic mixture of R and S enantiomers, both active, though not equally, and both metabolized via different routes. The S-warfarin is 3 to 5 times more potent than the R-enantiomer. Warfarin is metabolized, mainly in the liver, by several cytochrome P450 phase I biot

Pathway Diagram:

Elsevier Inc. UGT1A9 CYP2C18 (R)-warfarin (S)-warfarin 8-hydroxywarfarin ---> 8-OH-warf-gluc 7-hydroxywarfarin ---> 7-OH-warf-gluc 6-hydroxywarfarin ---> 6-OH-warf-gluc 4-hydroxywarfarin ---> 4-OH-warf-gluc UGT1A10 (S)-warfarin ---> 7-hydroxywarfarin (R)-warfarin ---> 10-hydroxywarfarin UGT1A8 UGT1A1 CYP2C19 CYP2C9 CYP2C8 CYP1A1 CYP1A2 CYP3A4 8-OH-warf-gluc 7-OH-warf-gluc 4-OH-warf-gluc 6-OH-warf-gluc 4-hydroxywarfarin 8-hydroxywarfarin 6-hydroxywarfarin 7-hydroxywarfarin 10-hydroxywarfarin 10-hydroxywarfarin ---| CYP2C9 7-hydroxywarfarin ---| CYP2C9 (S)-warfarin ---> 6-hydroxywarfarin (R)-warfarin ---> 6-hydroxywarfarin (R)-warfarin ---> 7-hydroxywarfarin (R)-warfarin ---> 8-hydroxywarfarin (R)-warfarin ---> 4-hydroxywarfarin
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Genes in Pathway:

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warfarin pharmacokinetics pathway term browser
Symbol Object Name Evidence Notes Source PubMed Reference(s) RGD Reference(s) Position
G Cyp1a1 cytochrome P450, family 1, subfamily a, polypeptide 1 ISO RGD PMID:26655108 RGD:11354883 NCBI chr 8:62,472,087...62,478,122
Ensembl chr 8:62,472,095...62,478,147
JBrowse link
G Cyp1a2 cytochrome P450, family 1, subfamily a, polypeptide 2 ISO RGD PMID:26655108 RGD:11354883 NCBI chr 8:62,451,360...62,458,244
Ensembl chr 8:62,451,329...62,458,301
JBrowse link
G Cyp2c24 cytochrome P450, family 2, subfamily c, polypeptide 24 ISO RGD PMID:26655108 RGD:11354883 NCBI chr 1:258,074,797...258,139,176
Ensembl chr 1:258,074,860...258,139,176
JBrowse link
G Cyp2c6v1 cytochrome P450, family 2, subfamily C, polypeptide 6, variant 1 ISO RGD PMID:26655108 RGD:11354883 NCBI chr 1:147,713,879...147,814,410
Ensembl chr 1:147,713,892...147,888,007
JBrowse link
G Cyp2c79 cytochrome P450, family 2, subfamily c, polypeptide 79 ISO RGD PMID:26655108 RGD:11354883 NCBI chr 1:147,236,480...147,307,988 JBrowse link
G Ugt1a1 UDP glucuronosyltransferase family 1 member A1 ISO RGD PMID:17921187 RGD:11354886 NCBI chr 9:95,295,701...95,302,822
Ensembl chr 9:95,161,157...95,302,822
JBrowse link
G Ugt1a8 UDP glucuronosyltransferase family 1 member A8 ISO RGD PMID:17921187 RGD:11354886 NCBI chr 9:95,221,474...95,302,822
Ensembl chr 9:95,161,157...95,302,822
JBrowse link
G Ugt1a9 UDP glucuronosyltransferase family 1 member A9 ISO RGD PMID:17921187 RGD:11354886 NCBI chr 9:95,161,157...95,302,822
Ensembl chr 9:95,161,157...95,302,822
JBrowse link

Pathway Gene Annotations

Disease Annotations Associated with Genes in the warfarin pharmacokinetics pathway
Disease TermsGene Symbols
acute kidney failureCyp1a1 , Cyp1a2 , Cyp2c6v1 , Ugt1a1 , Ugt1a9
Acute Liver FailureUgt1a1
Acute Lung InjuryCyp1a1
acute lymphoblastic leukemiaCyp1a1 , Cyp1a2 , Cyp2c79
acute myeloid leukemiaCyp1a1
allergic contact dermatitisCyp1a1
allergic diseaseCyp1a1
Allergic RhinoconjunctivitisCyp2c6v1
ankylosing spondylitisCyp1a1
ArteritisCyp1a1
asthmaCyp1a1
atopic dermatitisCyp1a1
atrial fibrillationCyp2c6v1
AtrophyCyp1a2
Behcet's diseaseCyp1a1
biliary tract cancerCyp1a1
bilirubin metabolic disorderUgt1a1 , Ugt1a8 , Ugt1a9
Birth WeightCyp1a1
BradycardiaCyp1a1
breast cancerCyp1a1 , Cyp1a2 , Ugt1a1
Breast NeoplasmsCyp1a1
bronchitisCyp1a1
CardiomegalyCyp1a1
cardiovascular system diseaseCyp2c6v1
Chemical and Drug Induced Liver InjuryCyp1a2 , Cyp2c6v1 , Ugt1a1 , Ugt1a9
cholangiocarcinomaUgt1a9
cholecystolithiasisUgt1a1
cholelithiasisUgt1a1
cholestasisCyp1a2 , Ugt1a1
Chronic BronchitisCyp1a1
chronic myeloid leukemiaCyp1a1
chronic obstructive pulmonary diseaseCyp1a1 , Cyp1a2
clubfootCyp1a1
colitisCyp1a1
Colorectal NeoplasmsCyp1a2
contact dermatitisCyp1a1 , Ugt1a1
Crigler Najjar Syndrome, Type 2Ugt1a1 , Ugt1a8 , Ugt1a9
Crigler-Najjar syndromeUgt1a1 , Ugt1a8 , Ugt1a9
Crohn's diseaseUgt1a1
cystic fibrosisCyp1a1
diabetes mellitusCyp1a1
Diabetes Mellitus, Experimental Cyp1a1
Digestive System NeoplasmsCyp1a1
Drug EruptionsCyp1a1 , Cyp2c6v1
Drug-Induced LeukopeniaCyp2c79
Drug-induced NeutropeniaCyp2c79 , Ugt1a1
Drug-Related Side Effects and Adverse ReactionsCyp1a2 , Cyp2c79 , Ugt1a1
end stage renal diseaseCyp1a1 , Cyp2c6v1 , Cyp2c79
endometrial cancerCyp1a1 , Cyp1a2 , Ugt1a1
endometriosisCyp1a1
eosinophilic esophagitisCyp2c6v1
esophageal cancerCyp1a1
esophagus squamous cell carcinomaCyp1a1
Experimental Liver CirrhosisCyp1a2
Experimental Liver NeoplasmsCyp1a1 , Cyp1a2 , Cyp2c79
Fetal Growth RetardationCyp1a1
gallbladder cancerCyp1a1
GallstonesUgt1a1
genetic diseaseUgt1a1 , Ugt1a8 , Ugt1a9
Genetic Predisposition to DiseaseCyp2c6v1
Gilbert syndromeUgt1a1 , Ugt1a8 , Ugt1a9
gliosarcomaCyp2c24
Gram-Negative Bacterial InfectionsUgt1a1
Graves' diseaseCyp1a1
Growth DisordersCyp1a2
HamartomaCyp1a1
head and neck cancerCyp1a1
heart diseaseCyp1a1
Hematologic NeoplasmsCyp2c6v1
hematopoietic system diseaseUgt1a1
hepatitis BUgt1a1
hepatocellular carcinomaCyp1a1 , Cyp1a2 , Cyp2c79
HepatomegalyCyp1a1 , Cyp1a2
Hereditary HyperbilirubinemiaUgt1a1
Hodgkin's lymphomaUgt1a1
Hyperbilirubinemia, Transient Familial NeonatalUgt1a1 , Ugt1a8 , Ugt1a9
HyperoxiaCyp1a1
Hyperoxic Lung InjuryCyp1a1
hypertensionCyp1a1
hyperthyroidismUgt1a1
hypospadiasCyp1a1
InflammationCyp1a1 , Ugt1a1
JaundiceCyp1a1 , Cyp1a2 , Ugt1a1
kernicterusUgt1a1
kidney diseaseCyp2c79
Kidney NeoplasmsCyp1a1
liver cirrhosisCyp1a2
liver diseaseCyp1a2
Liver InjuryCyp1a2
Liver Reperfusion InjuryCyp1a1
long QT syndromeCyp1a1
lung cancerCyp1a1
Lung InjuryCyp1a1 , Cyp1a2
Lung NeoplasmsCyp1a2
lung non-small cell carcinomaUgt1a1
male infertilityCyp1a1
mental depressionCyp1a2
methemoglobinemiaCyp1a2
Micronuclei, Chromosome-DefectiveCyp1a1
multiple myelomaCyp1a1 , Cyp2c6v1
myeloid leukemiaUgt1a1
Nematode InfectionsCyp1a1
Neonatal HyperbilirubinemiaUgt1a1
nephritisCyp1a1
nervous system diseaseCyp2c79
neural tube defectCyp1a2
neutropeniaUgt1a1
non-alcoholic fatty liver diseaseCyp1a2
Occupational DiseasesCyp1a1
oral cavity cancerCyp1a1
oral squamous cell carcinomaCyp1a1
ovarian cancerUgt1a1
Parkinson's diseaseCyp1a1
Parkinsonian DisordersCyp1a1
periodontitisCyp1a1
peripheral nervous system diseaseCyp2c79
peripheral vascular diseaseCyp1a1
pneumoniaCyp1a1
polycystic ovary syndromeCyp1a1
Poor Drug Metabolism, CYP2C19-RelatedCyp2c6v1
porphyria cutanea tardaCyp1a1 , Cyp1a2
premature ovarian failureCyp2c6v1
Proguanil, Poor Metabolism ofCyp2c6v1
prostate cancerCyp1a1
Prostatic NeoplasmsCyp1a1 , Cyp2c24 , Cyp2c6v1
psoriasisCyp1a1
psoriatic arthritisCyp1a1
pulmonary hypertensionCyp1a1
reactive arthritisCyp1a1
renal cell carcinomaCyp1a1
renal hypertensionCyp2c79
RhabdomyolysisCyp2c79
Rhabdomyolysis, Cerivastatin-InducedCyp2c79
schizophreniaCyp1a1 , Cyp1a2
SepsisCyp1a1 , Cyp1a2
sickle cell anemiaCyp2c6v1
Sjogren's syndromeCyp1a1
small cell carcinomaUgt1a1
splenic diseaseCyp1a2
SplenomegalyCyp1a2
Spontaneous AbortionsCyp1a1
squamous cell carcinomaCyp1a2
StarvationUgt1a1
stomach cancerCyp1a1
systemic lupus erythematosusCyp1a1
Tachycardia, SinusCyp1a1
Tardive DyskinesiaCyp1a2
thrombosisCyp2c6v1
type 1 diabetes mellitusUgt1a1
type 2 diabetes mellitusCyp1a1 , Cyp1a2 , Ugt1a1
urinary bladder cancerCyp1a1
Pathway Annotations Associated with Genes in the warfarin pharmacokinetics pathway
Pathway TermsGene Symbols
acetylsalicylic acid pharmacodynamics pathwayCyp2c79
antipyrine drug pathwayCyp2c79
arachidonic acid metabolic pathwayCyp2c79
artemether pharmacokinetics pathwayUgt1a9
ascorbate and aldarate metabolic pathwayUgt1a1 , Ugt1a8 , Ugt1a9
axitinib pharmacokinetics pathwayCyp1a2 , Cyp2c6v1 , Ugt1a1
caffeine metabolic pathwayCyp1a2
caffeine pharmacokinetics pathwayCyp1a2 , Cyp2c79
carbamazepine pharmacokinetics pathwayCyp2c6v1 , Cyp2c79
celecoxib pharmacodynamics pathwayCyp2c79
citalopram pharmacodynamics pathwayCyp2c6v1
citalopram pharmacokinetics pathwayCyp2c6v1
clomipramine pharmacokinetics pathwayCyp1a2 , Cyp2c6v1
clopidogrel pharmacodynamics pathwayCyp1a2 , Cyp2c6v1
clopidogrel pharmacokinetics pathwayCyp1a2 , Cyp2c6v1
codeine and morphine pharmacodynamics pathwayUgt1a1 , Ugt1a8
codeine and morphine pharmacokinetics pathwayUgt1a1 , Ugt1a8
cyclophosphamide pharmacodynamics pathwayCyp2c6v1 , Cyp2c79
cyclophosphamide pharmacokinetics pathwayCyp2c6v1 , Cyp2c79
diclofenac pharmacodynamics pathwayCyp2c79
diflunisal pharmacodynamics pathwayCyp2c79
doxepin pharmacokinetics pathwayCyp1a2 , Cyp2c6v1
etodolac pharmacodynamics pathwayCyp2c79
etoposide pharmacodynamics pathwayUgt1a1
etoposide pharmacokinetics pathwayUgt1a1
fenoprofen pharmacodynamics pathwayCyp2c79
fluoxetine pharmacodynamics pathwayCyp2c6v1
fluoxetine pharmacokinetics pathwayCyp2c6v1
flurbiprofen pharmacodynamics pathwayCyp2c79
forkhead class A signaling pathwayCyp2c24
gefitinib pharmacokinetics pathwayCyp1a1
ibuprofen pharmacodynamics pathwayCyp2c6v1 , Cyp2c79 , Ugt1a1 , Ugt1a9
ibuprofen pharmacokinetics pathwayCyp2c6v1 , Cyp2c79 , Ugt1a1 , Ugt1a9
ifosfamide pharmacodynamics pathwayCyp2c79
ifosfamide pharmacokinetics pathwayCyp2c79
imipramine pharmacodynamics pathwayCyp1a2 , Cyp2c6v1
imipramine pharmacokinetics pathwayCyp1a2 , Cyp2c6v1
indometacin pharmacodynamics pathwayCyp2c79
indometacin pharmacodynamics pathwayCyp2c79
irinotecan pharmacodynamics pathwayUgt1a1 , Ugt1a9
irinotecan pharmacokinetics pathwayUgt1a1 , Ugt1a9
ketoprofen pharmacodynamics pathwayCyp2c79
ketorolac pharmacodynamics pathwayCyp2c79
leukotriene C4 synthase deficiency pathwayCyp2c79
lidocaine pharmacodynamics pathwayCyp1a2
lidocaine pharmacokinetics pathwayCyp1a2
linoleic acid metabolic pathwayCyp1a2
lornoxicam pharmacodynamics pathwayCyp2c79
losartan pharmacokinetics pathwayCyp2c79 , Ugt1a1
magnesium salicylate pharmacodynamics pathwayCyp2c79
mefenamic acid pharmacodynamics pathwayCyp2c79
meloxicam pharmacodynamics pathwayCyp2c79
methadone pharmacodynamics pathwayCyp2c6v1 , Cyp2c79
methadone pharmacokinetics pathwayCyp2c6v1 , Cyp2c79
mycophenolic acid pharmacokinetics pathwayCyp2c79 , Ugt1a8 , Ugt1a9
nabumetone pharmacodynamics pathwayCyp2c79
naproxen pharmacodynamics pathwayCyp2c79
nicotine pharmacodynamics pathwayUgt1a9
nicotine pharmacokinetics pathwayUgt1a9
O-linked glycan biosynthetic pathwayUgt1a1 , Ugt1a8 , Ugt1a9
paracetamol drug pathwayCyp2c79
paracetamol pharmacokinetics pathwayCyp1a2 , Ugt1a1 , Ugt1a9
pentose and glucuronate interconversion pathwayUgt1a1 , Ugt1a8 , Ugt1a9
phase I biotransformation pathway via cytochrome P450Cyp1a1 , Cyp1a2 , Ugt1a1 , Ugt1a8 , Ugt1a9
phenytoin pharmacodynamics pathwayCyp1a2 , Cyp2c6v1 , Ugt1a1 , Ugt1a9
piroxicam pharmacodynamics pathwayCyp2c79
porphyrin and chlorophyll metabolic pathwayUgt1a1 , Ugt1a8 , Ugt1a9
repaglinide pharmacokinetics pathwayCyp2c79
retinol metabolic pathwayCyp1a1 , Cyp1a2 , Ugt1a1 , Ugt1a8 , Ugt1a9
rosiglitazone pharmacokinetics pathwayCyp2c79
salicylic acid pharmacodynamics pathwayCyp2c79
sodium salicylate pharmacodynamics pathwayCyp2c79
sorafenib pharmacokinetics pathwayCyp2c79 , Ugt1a1 , Ugt1a9
starch and sucrose metabolic pathwayUgt1a1 , Ugt1a8 , Ugt1a9
statin pharmacokinetics pathwayCyp2c79 , Ugt1a1
steroid hormone biosynthetic pathwayCyp1a1 , Ugt1a1 , Ugt1a8 , Ugt1a9
sulindac pharmacodynamics pathwayCyp2c79
tamoxifen pharmacokinetics pathwayCyp1a1 , Cyp1a2 , Cyp2c6v1 , Cyp2c79 , Ugt1a1 , Ugt1a8 , Ugt1a9
tenoxicam pharmacodynamics pathwayCyp2c79
tiaprofenic acid pharmacodynamics pathwayCyp2c79
tolmetin pharmacodynamics pathwayCyp2c79
tramadol pharmacokinetics pathwayUgt1a8
tryptophan metabolic pathwayCyp1a1 , Cyp1a2
valdecoxib pharmacodynamics pathwayCyp2c79
venlafaxine pharmacokinetics pathwayCyp2c6v1
vitamin A deficiency pathwayUgt1a1
warfarin pharmacokinetics pathwayCyp1a1 , Cyp1a2 , Cyp2c24 , Cyp2c6v1 , Cyp2c79 , Ugt1a1 , Ugt1a8 , Ugt1a9
Phenotype Annotations Associated with Genes in the warfarin pharmacokinetics pathway
Phenotype TermsGene Symbols
increased circulating bilirubin levelUgt1a1

References Associated with the warfarin pharmacokinetics pathway:

Ontology Path Diagram:

paths to the root
paths to the root

Import into Pathway Studio:


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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.