PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
ketoconazole

2D structure

Overview

Generic Names: 2%; Ketocanazole; Ketoconazol; Ketoconazol [INN-Spanish]; Ketoconazole [Usan:Ban:Inn:Jan]; Ketoconazolum [INN-Latin]; ketoconazole
Trade Names: Extina; Fungarest; Fungoral; Ketoderm; Ketoisdin; Ketozole; Nizoral; Nizoral Cream; Nizoral Shampoo; Nizoral a-D; Nizoral a-D Shampoo; Orifungal; Orifungal M; Panfungol; Sebazole
PharmGKB Accession Id: PA450146

Description

Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. PubChem (source: Drug Bank)

Indication

For the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. (source: Drug Bank)

ATC Therapeutic Categories

  • D01AC:Imidazole and triazole derivatives
  • G01AF:Imidazole derivatives
  • J02AB:Imidazole derivatives

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. (source: Drug Bank)

Pharmacology

Ketoconazole, like clotrimazole, fluconazole, itraconazole, and miconazole, is an imidazole antifungal agent. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
Take with food. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (source: Drug Bank)

Protein Binding

99% (in vitro, plasma protein binding) (source: Drug Bank)

Absorption

Moderate (source: Drug Bank)

Toxicity

Hepatotoxicity, LD<sub>50</sub>=86 mg/kg (orally in rat) (source: Drug Bank)

Isomeric SMILES Code:

CC(=O)N1CCN(CC1)c2ccc(cc2)OC[C@@H]3CO[C@@](O3)(Cn4ccnc4)c5ccc(cc5Cl)Cl (source: Drug Bank)

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  • PD
  • PK
  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
ABCC2
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  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2B6
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  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP2C8
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  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  •   
  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
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  • PK
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP2E1
  •   
  •   
  • PK
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  • CO
  • PD
  • PK
  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
GSTA1
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  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
GSTA2
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  •   
  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
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  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
NR1I3
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  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
NR3C1
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  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Has annotations
SLCO1B1
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  • FA
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
TAT
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  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
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  • PK
  • FA
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Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
UGT1A7
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  • PK
  • FA
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Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
UGT1A9
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  • PK
  • FA
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Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
CYP51A1 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
docetaxel
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  • PK
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  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
donepezil
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  • PK
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
galantamine
  •   
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  • PK
  •   
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
hydrocodone
  •   
  •   
  • PK
  • FA
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
lorazepam
  •   
  •   
  • PK
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
terfenadine
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
zidovudine
  •   
  •   
  • PK
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation The imidazole increases the effect of the anticoagulant (source: Drug Bank)
alfentanil Uncurated Annotation The imidazole increases the effect and toxicity of alfentanil (source: Drug Bank)
alfuzosin Uncurated Annotation The antifungal increases the effect of alfuzosin (source: Drug Bank)
almotriptan Uncurated Annotation This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan (source: Drug Bank)
alprazolam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
aluminium Uncurated Annotation The antacid decreases the effect of the imidazole (source: Drug Bank)
amitriptyline Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
anisindione Uncurated Annotation The imidazole increases the effect of the anticoagulant (source: Drug Bank)
aprepitant Uncurated Annotation This CYP3A4 inhibitor increases the effect and toxicity of aprepitant (source: Drug Bank)
aripiprazole Uncurated Annotation The imidazole increases the effect of aripiprazole (source: Drug Bank)
astemizole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
atorvastatin Uncurated Annotation Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
bosentan Uncurated Annotation The imidazole increases the effect and toxicity of bosentan (source: Drug Bank)
budesonide Uncurated Annotation The imidazole increases levels/effect of budesonide (source: Drug Bank)
buspirone Uncurated Annotation The macrolide increases the effect and toxicity of buspirone (source: Drug Bank)
calcium Uncurated Annotation The antacid decreases the effect of the imidazole (source: Drug Bank)
carbamazepine Uncurated Annotation The imidazole increases the effect of carbamazepine (source: Drug Bank)
cerivastatin Uncurated Annotation Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
chlordiazepoxide Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
ciclesonide Uncurated Annotation Increased effects/toxicity of ciclesonide (source: Drug Bank)
cilostazol Uncurated Annotation The imidazole increases the effect of cilostazol (source: Drug Bank)
cimetidine Uncurated Annotation The anti-H2 decreases the absorption of the imidazole (source: Drug Bank)
cinacalcet Uncurated Annotation The imidazole increases the effect and toxicity of cinacalcet (source: Drug Bank)
cisapride Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
clonazepam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
clorazepate Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
cyclosporine Uncurated Annotation The imidazole increases the effect of immunosuppressant (source: Drug Bank)
darifenacin Uncurated Annotation This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank)
diazepam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
dicumarol Uncurated Annotation The imidazole increases the effect of the anticoagulant (source: Drug Bank)
dihydroergotamine Uncurated Annotation Possible ergotism and sever ischemia with this combination (source: Drug Bank)
docetaxel Uncurated Annotation The agent increases the serum levels and toxicity of docetaxel (source: Drug Bank)
dofetilide Uncurated Annotation This strong CYP3A4 inhibitor increases the effect and toxicity of dofetilide (source: Drug Bank)
eletriptan Uncurated Annotation This potent CYP3A4 inhibitor increases the effect and toxicity of the triptan (source: Drug Bank)
eplerenone Uncurated Annotation The imidazole increases the effect and toxicity of eplerenone (source: Drug Bank)
ergotamine Uncurated Annotation Possible ergotism and sever ischemia with this combination (source: Drug Bank)
erlotinib Uncurated Annotation This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank)
esomeprazole Uncurated Annotation The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
estazolam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
estradiol Uncurated Annotation This anti-infectious agent could decrease the effect of the oral contraceptive (source: Drug Bank)
ethinyl estradiol Uncurated Annotation This anti-infectious agent could decrease the effect of the oral contraceptive (source: Drug Bank)
everolimus Uncurated Annotation The imidazole increases everolimus levels/toxicity (source: Drug Bank)
famotidine Uncurated Annotation The anti-H2 decreases the absorption of the imidazole (source: Drug Bank)
fentanyl Uncurated Annotation The imidazole increases levels/toxicity of fentanyl (source: Drug Bank)
flurazepam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
galantamine Uncurated Annotation Ketoconazole increases the effect and toxicity of galantamine (source: Drug Bank)
gefitinib Uncurated Annotation This CYP3A4 inhibitor increases levels/toxicity of gefitinib (source: Drug Bank)
halazepam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
haloperidol Uncurated Annotation The imidazole increases the effect and toxicity of haloperidol (source: Drug Bank)
imatinib Uncurated Annotation The imidazole increases the levels of imatinib (source: Drug Bank)
imipramine Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
indinavir Uncurated Annotation Ketoconazole increases the effect of indinavir (source: Drug Bank)
irinotecan Uncurated Annotation Ketoconazole increases the effect and toxicity of irinotecan (source: Drug Bank)
isoniazid Uncurated Annotation Isoniazid decreases the effect of ketoconazole (source: Drug Bank)
lansoprazole Uncurated Annotation The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
lovastatin Uncurated Annotation Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
magnesium Uncurated Annotation The antacid decreases the effect of the imidazole (source: Drug Bank)
magnesium Uncurated Annotation The antacid decreases the effect of the imidazole (source: Drug Bank)
magnesium oxide Uncurated Annotation The antacid decreases the effect of the imidazole (source: Drug Bank)
mestranol Uncurated Annotation This anti-infectious agent could decrease the effect of the oral contraceptive (source: Drug Bank)
methylprednisolone Uncurated Annotation The imidazole increases the effect and toxicity of the corticosteroid (source: Drug Bank)
midazolam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
nevirapine Uncurated Annotation Nevirapine decreases the effect of ketoconazole (source: Drug Bank)
nizatidine Uncurated Annotation The anti-H2 decreases the absorption of the imidazole (source: Drug Bank)
nortriptyline Uncurated Annotation The imidazole increases the effect and toxicity of the tricyclic (source: Drug Bank)
omeprazole Uncurated Annotation The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
pantoprazole Uncurated Annotation The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
pimozide Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
pioglitazone Uncurated Annotation Ketoconazole increases the effect of pioglitazone (source: Drug Bank)
prednisolone Uncurated Annotation The imidazole increases the effect and toxicity of the corticosteroid (source: Drug Bank)
prednisone Uncurated Annotation The imidazole increases the effect and toxicity of the corticosteroid (source: Drug Bank)
quazepam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
quetiapine Uncurated Annotation Ketoconazole increases the effect/toxicity of quetiapine (source: Drug Bank)
quinidine Uncurated Annotation The imidazole increases the effect and toxicity of quinidine (source: Drug Bank)
quinidine Uncurated Annotation The imidazole increases the effect and toxicity of quinidine (source: Drug Bank)
rabeprazole Uncurated Annotation The proton pump inhibitor decreases the absorption of imidazole (source: Drug Bank)
ramelteon Uncurated Annotation The imidazole increases the levels/toxicity of ramelteon (source: Drug Bank)
ranitidine Uncurated Annotation The anti-H2 decreases the absorption of the imidazole (source: Drug Bank)
ranolazine Uncurated Annotation Increased levels of ranolazine - risk of toxicity (source: Drug Bank)
rifampin Uncurated Annotation Rifampin dereases the effect of the imidazole (source: Drug Bank)
ritonavir Uncurated Annotation The imidazole increases the effect and toxicity of ritonavir (source: Drug Bank)
rosiglitazone Uncurated Annotation Ketoconazole increases the effect of rosiglitazone (source: Drug Bank)
saquinavir Uncurated Annotation The imidazole increases the effect and toxicity of saquinavir (source: Drug Bank)
sibutramine Uncurated Annotation Ketoconazole increases the levels and toxicity of sibutramine (source: Drug Bank)
sildenafil Uncurated Annotation The imidazole increases the effect and toxicity of sildenafil (source: Drug Bank)
simvastatin Uncurated Annotation Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
sirolimus Uncurated Annotation The imidazole increases the effect and toxicity of sirolimus (source: Drug Bank)
solifenacin Uncurated Annotation This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank)
sucralfate Uncurated Annotation Sucralfate decreases the absorption of the imidazole (source: Drug Bank)
sunitinib Uncurated Annotation Possible increase in sunitinib levels (source: Drug Bank)
tacrolimus Uncurated Annotation The imidazole increases the effect of immunosuppressant (source: Drug Bank)
tadalafil Uncurated Annotation The imidazole increases tadalafil levels (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
tolbutamide Uncurated Annotation Ketoconazole increases the effect and toxicity of tolbutamide (source: Drug Bank)
tolterodine Uncurated Annotation The imidazole increases the effect and toxicity of tolterodine (source: Drug Bank)
trazodone Uncurated Annotation This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone (source: Drug Bank)
triazolam Uncurated Annotation The imidazole increases the effect of the benzodiazepine (source: Drug Bank)
valdecoxib Uncurated Annotation The imidazole increases the effect and toxicity of valdecoxib (source: Drug Bank)
vardenafil Uncurated Annotation The imidazole increases the effect and toxicity of vardenafil (source: Drug Bank)
vinblastine Uncurated Annotation The imidazole increases the effect and toxicity of vinblastine (source: Drug Bank)
vincristine Uncurated Annotation The imidazole increases the effect and toxicity of the antineoplasic (source: Drug Bank)
warfarin Uncurated Annotation The imidazole increases the effect of the anticoagulant (source: Drug Bank)
ziprasidone Uncurated Annotation Ketoconazole increases the effect and toxicity of ziprasidone (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Drug Toxicity
  • CO
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Osteosarcoma
  •   
  •   
  •   
  • FA
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Drug-Induced Long QT Intervals
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Dan Roden, MD involving ADRB1, ADRB2, KCNE1, KCNE2, KCNH2, KCNQ1, SCN5A, almokalant, amiodarone, amitriptyline, bretylium, bupivacaine, cisapride, disopyramide, dofetilide, encainide, fluconazole, haloperidol, hydroquinidine, isoflurane, itraconazole, ketoconazole, lithium, loratadine, metoclopramide, nortriptyline, procainamide, quinidine, sematilide, sotalol, sulfamethoxazole, thioridazine, trimethoprim, , Long QT Syndrome, Proarrhythmia and Torsades de Pointes

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

Downloads

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LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01026
KEGG Drug ID:
D00351
PubChem Compound ID:
47576
PubChem Substance ID:
186839
IUPHAR Ligand ID:
2568

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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