Identification

Name
Ketoconazole
Accession Number
DB01026
Description

Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.Label It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.5,11 Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981.9 At this time it was considered a significant improvement over previous antifungals, miconazole and clotrimazole, due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.9,10 These effects combined with waning efficacy led to its eventual replacement by triazole agents, fluconazole, itraconazole, voriconazole, and posaconazole. Ketoconazole and its predecessor clotrimazole continue to be used in topical formulations.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 531.431
Monoisotopic: 530.148760818
Chemical Formula
C26H28Cl2N4O4
Synonyms
  • Ketoconazol
  • Ketoconazole
  • Ketoconazolum
  • Ketozole
External IDs
  • KW-1414
  • R 41,400
  • R-41400

Pharmacology

Indication

Ketoconazole is used in the treatment or prevention of fungal infections including blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.Label In Europe, it is also used in the treatment of endogenous Cushing's syndrome.12

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Ketoconazole, similarly to other azole antifungals, is a fungistatic agent which causes growth arrest in fungal cells thereby preventing growth and spread of the fungus throughout the body.11

Mechanism of action

Ketoconazole interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol.5,11 This results in inhibition of ergosterol synthesis and increased fungal cellular permeability due to reduced amounts of ergosterol present in the fungal cell membrane. This metabolic inhibition also results in accumulation of 14α-methyl-3,6-diol, a toxic metabolite. The increase in membrane fluidity is also thought to produce impairment of membrane-bound enzyme systems as components become less closely packed.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
UAndrogen receptor
binder
Humans
ASteroid 17-alpha-hydroxylase/17,20 lyase
inhibitor
Humans
USteroid 21-hydroxylase
inhibitor
Humans
UPotassium voltage-gated channel subfamily H member 2
inhibitor
Humans
UNuclear receptor subfamily 1 group I member 2
antagonist
Humans
UNuclear receptor subfamily 1 group I member 3Not AvailableHumans
Absorption

Ketoconazole requires an acidic environment to become soluble in water.6 At pH values above 3 it becomes increasingly insoluble with about 10% entering solution in 1 h. At pH less than 3 dissolution is 85% complete in 5 min and entirely complete within 30 min. A single 200 mg oral dose produces a Cmax of 2.5-3 mcg/mL with a Tmax of 1-4 h.5,13 Administering ketoconazole with food consistently increases Cmax and delays Tmax but literature is contradictory regarding the effect on AUC, which may experience a small decrease.5,6 A bioavailablity of 76% has been reported for ketoconazole.5

Volume of distribution

Ketoconazole has an estimated volume of distribution of 25.41 L or 0.36 L/kg.5 It distributes widely among the tissues, reaching effective concentrations in the skin, tendons, tears, and saliva.6 Distribution to vaginal tissue produces concentrations 2.4 times lower than plasma. Penetration into the CNS, bone, and seminal fluid are minimal. Ketoconazole has been found to enter the breast milk and cross the placenta in animal studies.5

Protein binding

Ketoconazole is approximately 84% bound to plasma albumin with another 15% associated with blood cells for a total of 99% binding within the plasma.5

Metabolism

The major metabolite of ketoconazole appears to be M2, an end product resulting from oxidation of the imidazole moiety.8 CYP3A4 is known to be the primary contributor to this reaction with some contribution from CYP2D6. Other metabolites resulting from CYP3A4 mediated oxidation of the imidazole moiety include M3, M4, and M5. Ketoconazole may also undergo N-deacetylation to M14, , alkyl oxidation to M7, N-oxidation to M13, or aromatic hydroxylation to M8, or hydroxylation to M9. M9 may further undergo oxidation of the hydroxyl to form M12, N-dealkylation to form M10 with a subsequent N-dealkylation to M15, or may form an iminium ion. No metabolites are known to be active however oxidation metabolites of M14 have been implicated in cytotoxicity.

Hover over products below to view reaction partners

Route of elimination

Only 2-4% of the ketoconazole dose is eliminated unchanged in the urine.5 Over 95% is eliminated through hepatic metabolism.

Half-life

Ketoconazole experiences biphasic elimination with the first phase having a half-life of 2 hours and a terminal half life of 8 hours.5

Clearance

Ketoconazole has an estimated clearance of 8.66 L/h.5

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Symptoms of overdose include acute liver injury, which may include both hepatocellular and cholestatic injury, accompanied by anorexia, fatigue, nausea, and jaundice.14,7 In case of overdose, gastric lavage with activated charcoal may be used if within one hour of ketoconazole ingestion otherwise provide supportive care.Label,12 If the patient shows signs of adrenal insufficiency, administer 100 mg hydrocortisone once together with saline and glucose infusion and monitor the patient closely. Blood pressure and fluid and electrolyte balance should be monitored over the next few days.12

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirThe metabolism of Abacavir can be decreased when combined with Ketoconazole.
AbametapirThe serum concentration of Ketoconazole can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Ketoconazole.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Ketoconazole.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Ketoconazole.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Ketoconazole.
AceclofenacThe risk or severity of hyperkalemia can be increased when Ketoconazole is combined with Aceclofenac.
AcemetacinThe metabolism of Acemetacin can be decreased when combined with Ketoconazole.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ketoconazole.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Ketoconazole.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol. Drinking alcohol while on ketoconazole treatment may cause liver injury.
  • Avoid multivalent ions. They may decrease ketoconazole concentrations.
  • Take with food. Food decreases gastrointestinal irritation caused by ketoconazole.

Products

Product Images
International/Other Brands
Fungarest (Janssen-Cilag) / Fungoral (Johnson & Johnson) / Ketoderm (Hessel) / Ketoisdin (Isdin) / Ketozole (Ranbaxy) / Nizoral Cream (Ortho-McNeil) / Nizoral Shampoo (Ortho-McNeil) / Orifungal (Janssen) / Orifungal M (Janssen) / Panfungol (Esteve)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ExtinaAerosol, foam20 mg/1gTopicalMylan Pharmaceuticals Inc.2019-01-04Not applicableUS flag
ExtinaAerosol, foam20 mg/1gTopicalPrestium Pharma, Inc.2014-01-102019-05-31US flag
ExtinaAerosol, foam20 mg/1gTopicalStiefel Laboratories, Inc.2007-07-012014-06-30US flag
Ketoderm Cream 2%CreamTopicalTaropharma, A Division Of Taro Pharmaceuticals Inc.2002-05-23Not applicableCanada flag
NizoralShampoo20 mg/1mLTopicalJanssen Pharmaceuticals, Inc.1990-08-312025-04-30US flag
NizoralShampoo20 mg/1mLTopicalA S Medication Solutions1990-08-31Not applicableUS flag
NizoralShampoo20 mg/1mLTopicalPhysicians Total Care, Inc.1994-04-132011-06-30US flag
NizoralTablet200 mg/1OralJanssen Pharmaceuticals1981-06-122007-06-30US flag
NizoralShampoo20 mg/1mLTopicalMc Neil Consumer Healthcare Div. Mc Neil Ppc, Inc1990-08-312010-11-30US flag
NizoralTablet200 mg/1OralPhysicians Total Care, Inc.1991-07-312007-12-31US flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-ketoconazoleTabletOralApotex Corporation1998-02-03Not applicableCanada flag
KetaconazoleAerosol, foam20 mg/1gTopicalMylan Pharmaceuticals Inc.2018-12-20Not applicableUS flag
KetoconazoleTablet200 mg/1OralNucare Pharmaceuticals,inc.2018-06-26Not applicableUS flag
KetoconazoleTablet200 mg/1OralMutual Pharmaceutical1999-06-152011-09-30US flag
KetoconazoleCream20 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2002-12-18Not applicableUS flag
KetoconazoleAerosol, foam2 g/100gTopicalPerrigo New York Inc2011-08-30Not applicableUS flag
KetoconazoleTablet200 mg/1OralRebel Distributors1999-06-15Not applicableUS flag
KetoconazoleCream20 mg/1gTopicalA-S Medication Solutions2002-12-182019-07-31US flag
KetoconazoleCream20 mg/1gTopicalNucare Pharmaceuticals,inc.2002-12-182020-03-31US flag
KetoconazoleShampoo, suspension20 mg/1mLTopicalPreferred Pharmaceuticals, Inc.2012-01-30Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
NizoralShampoo10 mg/1mLTopicalKramer Laboratories2019-01-07Not applicableUS flag
NizoralShampoo10 mg/1mLTopicalKramer Laboratories2019-01-07Not applicableUS flag
NizoralShampoo2 %TopicalKramer Laboratories, Inc1990-12-30Not applicableCanada flag
Nizoral A-DShampoo10 mg/1mLTopicalJohnson & Johnson Consumer Inc., McNeil Consumer Healthcare Division1999-04-01Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
KetoconKetoconazole (20 mg/1g) + Hydrocortisone (10 mg/1g)KitTopicalTiber Laboratories, LLC2011-04-062012-06-30US flag
PedizolPAKKetoconazole (20 mg/1g) + Miconazole nitrate (20 mg/1mL)TopicalNucare Pharmaceuticals,inc.2002-12-18Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Hydrocortisone 2.5% / Iodoquinol 1% / Ketoconazole 2%Ketoconazole (2 g/100g) + Diiodohydroxyquinoline (1 g/100g) + Hydrocortisone (2.5 g/100g)CreamTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag
Hydrocortisone 2.5% / Ketoconazole 2%Ketoconazole (2 g/100g) + Hydrocortisone (2.5 g/100g)CreamTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag
Ketoconazole 2% / Niacinamide 4%Ketoconazole (2 g/100g) + Nicotinamide (4 g/100g)CreamTopicalSincerus Florida LLC2019-05-13Not applicableUS flag
Ketoconazole 2% / Salicylic Acid 2%Ketoconazole (2 g/100g) + Salicylic acid (2 g/100g)ShampooTopicalSincerus Florida, LLC2019-05-17Not applicableUS flag

Categories

ATC Codes
G01AF11 — KetoconazoleG01AF20 — Combinations of imidazole derivativesJ02AB02 — KetoconazoleD01AC08 — Ketoconazole
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Phenylpiperazines
Alternative Parents
N-arylpiperazines / Aminophenyl ethers / Phenoxy compounds / Aniline and substituted anilines / Dialkylarylamines / Dichlorobenzenes / Alkyl aryl ethers / Ketals / Aryl chlorides / N-substituted imidazoles
show 12 more
Substituents
1,3-dichlorobenzene / Acetal / Acetamide / Alkyl aryl ether / Amine / Amino acid or derivatives / Aminophenyl ether / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl chloride
show 34 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
N-arylpiperazine, imidazoles, ether, dioxolane, dichlorobenzene, N-carbonylpiperazine (CHEBI:48339) / a small molecule (CPD-4503)

Chemical Identifiers

UNII
R9400W927I
CAS number
65277-42-1
InChI Key
XMAYWYJOQHXEEK-UHFFFAOYSA-N
InChI
InChI=1S/C26H28Cl2N4O4/c1-19(33)31-10-12-32(13-11-31)21-3-5-22(6-4-21)34-15-23-16-35-26(36-23,17-30-9-8-29-18-30)24-7-2-20(27)14-25(24)28/h2-9,14,18,23H,10-13,15-17H2,1H3
IUPAC Name
1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethan-1-one
SMILES
CC(=O)N1CCN(CC1)C1=CC=C(OCC2COC(CN3C=CN=C3)(O2)C2=CC=C(Cl)C=C2Cl)C=C1

References

Synthesis Reference

U.S. Patent 4,144,346.

General References
  1. Goeders NE, Peltier RL, Guerin GF: Ketoconazole reduces low dose cocaine self-administration in rats. Drug Alcohol Depend. 1998 Dec 1;53(1):67-77. [PubMed:10933341]
  2. Berwaerts J, Verhelst J, Mahler C, Abs R: Cushing's syndrome in pregnancy treated by ketoconazole: case report and review of the literature. Gynecol Endocrinol. 1999 Jun;13(3):175-82. [PubMed:10451809]
  3. Kazy Z, Puho E, Czeizel AE: Population-based case-control study of oral ketoconazole treatment for birth outcomes. Congenit Anom (Kyoto). 2005 Mar;45(1):5-8. [PubMed:15737124]
  4. Pierard-Franchimont C, Goffin V, Decroix J, Pierard GE: A multicenter randomized trial of ketoconazole 2% and zinc pyrithione 1% shampoos in severe dandruff and seborrheic dermatitis. Skin Pharmacol Appl Skin Physiol. 2002 Nov-Dec;15(6):434-41. [PubMed:12476017]
  5. Van Tyle JH: Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use. Pharmacotherapy. 1984 Nov-Dec;4(6):343-73. [PubMed:6151171]
  6. Daneshmend TK, Warnock DW: Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet. 1988 Jan;14(1):13-34. doi: 10.2165/00003088-198814010-00002. [PubMed:3280211]
  7. Kim TH, Kim BH, Kim YW, Yang DM, Han YS, Dong SH, Kim HJ, Chang YW, Lee JI, Chang R: Liver cirrhosis developed after ketoconazole-induced acute hepatic injury. J Gastroenterol Hepatol. 2003 Dec;18(12):1426-9. doi: 10.1046/j.1440-1746.2003.02852.x. [PubMed:14675275]
  8. Fitch WL, Tran T, Young M, Liu L, Chen Y: Revisiting the metabolism of ketoconazole using accurate mass. Drug Metab Lett. 2009 Aug;3(3):191-8. [PubMed:19799546]
  9. Maertens JA: History of the development of azole derivatives. Clin Microbiol Infect. 2004 Mar;10 Suppl 1:1-10. doi: 10.1111/j.1470-9465.2004.00841.x. [PubMed:14748798]
  10. Gupta AK, Lyons DC: The Rise and Fall of Oral Ketoconazole. J Cutan Med Surg. 2015 Jul-Aug;19(4):352-7. doi: 10.1177/1203475415574970. Epub 2015 Mar 5. [PubMed:25775613]
  11. Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  12. EMA SmPC: Ketoconazole [Link]
  13. FDA Label: Ketoconazole Tablets [Link]
  14. HSDB: Ketoconazole [Link]
  15. Ketoconazole FDA Label [Link]
  16. CPHI Online: Front-2 Ovules (clindamycin/ketoconazole) for vaginal use [Link]
KEGG Drug
D00351
PubChem Compound
3823
PubChem Substance
46506746
ChemSpider
3691
BindingDB
151585
RxNav
6135
ChEBI
48339
ChEMBL
CHEMBL157101
Therapeutic Targets Database
DAP000630
PharmGKB
PA450146
PDBe Ligand
KTN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ketoconazole
AHFS Codes
  • 84:04.08.08 — Azoles
  • 08:14.08 — Azoles
FDA label
Download (222 KB)
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceTransplantation, Kidney1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentPityriasis versicolor1
4CompletedTreatmentPityrosporum Folliculitis1
4CompletedTreatmentSeborrheic Dermatitis1
3CompletedTreatmentBacterial Vaginosis (BV) / Vulvovaginal Candidiasis1
3CompletedTreatmentChronic Lung Diseases / Respiratory Distress Syndrome, Adult1
3CompletedTreatmentPost - Adolescence Acne1
3CompletedTreatmentProstate Cancer4
3CompletedTreatmentScalp Seborrheic Dermatitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Apical Pharmaceutical Corporation
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • DAVA Pharmaceuticals
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • DPT Laboratories Ltd.
  • E. Fougera and Co.
  • H.J. Harkins Co. Inc.
  • Janssen-Ortho Inc.
  • JSJ Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • McNeil Laboratories
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Nycomed Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • Patriot Pharmaceuticals
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Perrigo Co.
  • Pharma Pac LLC
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prescript Pharmaceuticals
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandoz
  • Stiefel Labs
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Tolmar Inc.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • United Research Laboratories Inc.
Dosage Forms
FormRouteStrength
InsertVaginal100 mg
CreamTopical0.04 g
Aerosol, foamTopical20 mg/1g
EmulsionTopical2 g
EmulsionTopical1 g
Solution
Tablet, coatedOral200 mg
Shampoo20 mg/ml
KitTopical
Aerosol, foamTopical2 g/100g
CreamTopical20 mg/1
CreamTopical20 mg/1g
Shampoo, suspensionTopical20 mg/1mL
Shampoo, suspensionTopical20.5 mg/1mL
TabletOral200 mg/1
CreamTopical
ShampooTopical
KitTopical20 mg/1g
Cream2 %
CreamTopical
EmulsionTopical2000 mg
TabletOral200 mg
Shampoo2 %
Tablet200 mg
SuppositoryVaginal400 mg
Suspension100 ml
Suspension30 ml
CreamTopical20 mg/g
ShampooTopical10 mg/1mL
ShampooTopical2 %
ShampooTopical20 mg/1mL
SuspensionOral
ShampooTopical
CreamTopical2 g
Shampoo
Cream
CreamTopical2 %
TabletOral
CreamTopical2.04 g
GelTopical2 %
GelTopical20 mg/1g
Tablet
Prices
Unit descriptionCostUnit
Extina 2% Foam 100 gm Can375.44USD can
Extina 2% Foam 50 gm Can201.53USD can
Nizoral 2% Shampoo 120ml Bottle49.43USD bottle
Ketoconazole 2% Cream 60 gm Tube44.72USD tube
Ketoconazole 2% Cream 30 gm Tube29.43USD tube
Ketoconazole 2% Shampoo 120ml Bottle27.98USD bottle
Ketoconazole 2% Cream 15 gm Tube19.99USD tube
Ketoconazole powder15.0USD g
Nizoral 200 mg tablet4.75USD tablet
Extina 2% foam3.61USD g
Ketoconazole 200 mg tablet3.21USD tablet
Kuric 2% cream1.54USD g
Apo-Ketoconazole 200 mg Tablet1.24USD tablet
Novo-Ketoconazole 200 mg Tablet1.24USD tablet
Nu-Ketocon 200 mg Tablet1.24USD tablet
Nizoral 2% cream1.22USD g
Ketoconazole 2% cream1.1USD g
Ketoderm 2 % Cream0.35USD g
Ketoconazole 2% shampoo0.23USD ml
Nizoral a-d 1% shampoo0.07USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5456851No1995-10-102014-04-07US flag
US7179475No2007-02-202018-12-04US flag
US8232276No2012-07-312020-11-24US flag
US8735393No2014-05-272018-12-04US flag
US7553835No2009-06-302018-10-19US flag
US8026238No2011-09-272018-10-19US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)146U.S. Patent 4,144,346.
logP4.35SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.00931 mg/mLALOGPS
logP4.3ALOGPS
logP4.19ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)6.75ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area69.06 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity138.07 m3·mol-1ChemAxon
Polarizability54.83 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.6704
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7293
P-glycoprotein inhibitor IInhibitor0.8389
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterNon-inhibitor0.5644
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.7409
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9386
Ames testNon AMES toxic0.7003
CarcinogenicityNon-carcinogens0.8836
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.4739 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9258
hERG inhibition (predictor II)Inhibitor0.8403
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity).
Gene Name
ERG11
Uniprot ID
P50859
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
61304.95 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Agut J, Palacin C, Sacristan A, Ortiz JA: Inhibition of ergosterol synthesis by sertaconazole in Candida albicans. Arzneimittelforschung. 1992 May;42(5A):718-20. [PubMed:1627190]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  5. Agut J, Palacin C, Salgado J, Casas E, Sacristan A, Ortiz JA: Direct membrane-damaging effect of sertaconazole on Candida albicans as a mechanism of its fungicidal activity. Arzneimittelforschung. 1992 May;42(5A):721-4. [PubMed:1627191]
  6. Croxtall JD, Plosker GL: Sertaconazole: a review of its use in the management of superficial mycoses in dermatology and gynaecology. Drugs. 2009;69(3):339-59. doi: 10.2165/00003495-200969030-00009. [PubMed:19275277]
  7. Borgers M, Degreef H, Cauwenbergh G: Fungal infections of the skin: infection process and antimycotic therapy. Curr Drug Targets. 2005 Dec;6(8):849-62. [PubMed:16375669]
  8. Warrilow AG, Martel CM, Parker JE, Melo N, Lamb DC, Nes WD, Kelly DE, Kelly SL: Azole binding properties of Candida albicans sterol 14-alpha demethylase (CaCYP51). Antimicrob Agents Chemother. 2010 Oct;54(10):4235-45. doi: 10.1128/AAC.00587-10. Epub 2010 Jul 12. [PubMed:20625155]
  9. FDA Label: Ketoconazole Tablets [Link]
  10. EMA SmPC: Ketoconazole [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Eil C: Ketoconazole binds to the human androgen receptor. Horm Metab Res. 1992 Aug;24(8):367-70. [PubMed:1526623]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Steroid 17-alpha-monooxygenase activity
Specific Function
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation ...
Gene Name
CYP17A1
Uniprot ID
P05093
Uniprot Name
Steroid 17-alpha-hydroxylase/17,20 lyase
Molecular Weight
57369.995 Da
References
  1. Trachtenberg J, Zadra J: Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5. [PubMed:2966691]
  2. EMA SmPC: Ketoconazole [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Specifically catalyzes the 21-hydroxylation of steroids. Required for the adrenal synthesis of mineralocorticoids and glucocorticoids.
Gene Name
CYP21A2
Uniprot ID
P08686
Uniprot Name
Steroid 21-hydroxylase
Molecular Weight
55886.805 Da
References
  1. Trachtenberg J, Zadra J: Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5. [PubMed:2966691]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the ...
Gene Name
KCNH2
Uniprot ID
Q12809
Uniprot Name
Potassium voltage-gated channel subfamily H member 2
Molecular Weight
126653.52 Da
References
  1. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [PubMed:15272206]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Svecova L, Vrzal R, Burysek L, Anzenbacherova E, Cerveny L, Grim J, Trejtnar F, Kunes J, Pour M, Staud F, Anzenbacher P, Dvorak Z, Pavek P: Azole antimycotics differentially affect rifampicin-induced pregnane X receptor-mediated CYP3A4 gene expression. Drug Metab Dispos. 2008 Feb;36(2):339-48. Epub 2007 Nov 12. [PubMed:17998298]
  2. Li H, Redinbo MR, Venkatesh M, Ekins S, Chaudhry A, Bloch N, Negassa A, Mukherjee P, Kalpana G, Mani S: Novel yeast-based strategy unveils antagonist binding regions on the nuclear xenobiotic receptor PXR. J Biol Chem. 2013 May 10;288(19):13655-68. doi: 10.1074/jbc.M113.455485. Epub 2013 Mar 22. [PubMed:23525103]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Curator comments
Inverse agonist at the canonical form of the receptor. Likely an antagonist at isoform 3 of the receptor.
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Sakaeda T, Iwaki K, Kakumoto M, Nishikawa M, Niwa T, Jin JS, Nakamura T, Nishiguchi K, Okamura N, Okumura K: Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1 activities, and its comparison with azole antifungal drugs. J Pharm Pharmacol. 2005 Jun;57(6):759-64. [PubMed:15969931]
  2. Elsherbiny ME, El-Kadi AO, Brocks DR: The metabolism of amiodarone by various CYP isoenzymes of human and rat, and the inhibitory influence of ketoconazole. J Pharm Pharm Sci. 2008;11(1):147-59. [PubMed:18445370]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Allqvist A, Miura J, Bertilsson L, Mirghani RA: Inhibition of CYP3A4 and CYP3A5 catalyzed metabolism of alprazolam and quinine by ketoconazole as racemate and four different enantiomers. Eur J Clin Pharmacol. 2007 Feb;63(2):173-9. doi: 10.1007/s00228-006-0230-z. Epub 2007 Jan 3. [PubMed:17200836]
  2. Shirasaka Y, Chang SY, Grubb MF, Peng CC, Thummel KE, Isoherranen N, Rodrigues AD: Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions. Drug Metab Dispos. 2013 Aug;41(8):1566-74. doi: 10.1124/dmd.112.049940. Epub 2013 May 30. [PubMed:23723360]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K: In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet. 2003;18(5):287-95. [PubMed:15618748]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
Found to induce the enzyme time-dependently in murine models but does not appear to have been confirmed in humans.
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  2. Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M: Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica. 2000 Apr;30(4):327-43. [PubMed:10821163]
  3. Korashy HM, Shayeganpour A, Brocks DR, El-Kadi AO: Induction of cytochrome P450 1A1 by ketoconazole and itraconazole but not fluconazole in murine and human hepatoma cell lines. Toxicol Sci. 2007 May;97(1):32-43. Epub 2007 Feb 5. [PubMed:17283379]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Shet MS, McPhaul M, Fisher CW, Stallings NR, Estabrook RW: Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos. 1997 Nov;25(11):1298-303. [PubMed:9351907]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Draper AJ, Madan A, Parkinson A: Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch Biochem Biophys. 1997 May 1;341(1):47-61. doi: 10.1006/abbi.1997.9964. [PubMed:9143352]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  2. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [PubMed:17101742]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  2. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  3. Park JY, Kim KA, Shin JG, Lee KY: Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. Br J Clin Pharmacol. 2004 Oct;58(4):397-402. doi: 10.1111/j.1365-2125.2004.02161.x. [PubMed:15373932]
  4. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO: The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000 Dec;50(6):573-80. doi: 10.1046/j.1365-2125.2000.00316.x. [PubMed:11136296]
  5. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Park JY, Kim KA, Shin JG, Lee KY: Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. Br J Clin Pharmacol. 2004 Oct;58(4):397-402. doi: 10.1111/j.1365-2125.2004.02161.x. [PubMed:15373932]
  2. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  3. McKillop D, Wild MJ, Butters CJ, Simcock C: Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53. doi: 10.1080/004982598239092 . [PubMed:9764927]
  4. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [PubMed:11854151]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K: In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet. 2003;18(5):287-95. [PubMed:15618748]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochro...
Gene Name
CYP11B1
Uniprot ID
P15538
Uniprot Name
Cytochrome P450 11B1, mitochondrial
Molecular Weight
57572.44 Da
References
  1. Denner K, Vogel R, Schmalix W, Doehmer J, Bernhardt R: Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 Chinese hamster cells and their application for testing of potential inhibitors. Pharmacogenetics. 1995 Apr;5(2):89-96. [PubMed:7663533]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A7
Uniprot ID
Q9HAW7
Uniprot Name
UDP-glucuronosyltransferase 1-7
Molecular Weight
59818.315 Da
References
  1. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Leukotriene-b4 20-monooxygenase activity
Specific Function
Catalyzes leukotriene B4 omega-hydroxylation and arachidonic acid omega-hydroxylation but with an activity much lower than that of CYP4F2. Catalyzes the hydroxylation of the antihistamine ebastine.
Gene Name
CYP4F12
Uniprot ID
Q9HCS2
Uniprot Name
Cytochrome P450 4F12
Molecular Weight
60269.165 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Weber MM, Will A, Adelmann B, Engelhardt D: Effect of ketoconazole on human ovarian C17,20-desmolase and aromatase. J Steroid Biochem Mol Biol. 1991 Feb;38(2):213-8. [PubMed:2004042]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Not Available
Specific Function
Not Available
Gene Name
CYP4F2
Uniprot ID
P78329
Uniprot Name
Phylloquinone omega-hydroxylase CYP4F2
Molecular Weight
59852.825 Da
References
  1. Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL: Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos. 2004 Jan;32(1):105-12. doi: 10.1124/dmd.32.1.105. [PubMed:14709627]
  2. Wang MZ, Saulter JY, Usuki E, Cheung YL, Hall M, Bridges AS, Loewen G, Parkinson OT, Stephens CE, Allen JL, Zeldin DC, Boykin DW, Tidwell RR, Parkinson A, Paine MF, Hall JE: CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime]. Drug Metab Dispos. 2006 Dec;34(12):1985-94. doi: 10.1124/dmd.106.010587. Epub 2006 Sep 22. [PubMed:16997912]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Daneshmend TK, Warnock DW: Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet. 1988 Jan;14(1):13-34. doi: 10.2165/00003088-198814010-00002. [PubMed:3280211]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Eil C: Ketoconazole binds to the human androgen receptor. Horm Metab Res. 1992 Aug;24(8):367-70. [PubMed:1526623]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [PubMed:10820137]
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
  3. Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW: Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother. 2002 Jan;46(1):160-5. [PubMed:11751127]
  4. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [PubMed:11961113]
  5. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [PubMed:12699389]
  6. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]
  7. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]
  8. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [PubMed:19319690]
  9. Takano M, Hasegawa R, Fukuda T, Yumoto R, Nagai J, Murakami T: Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. Eur J Pharmacol. 1998 Oct 9;358(3):289-94. [PubMed:9822896]
  10. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [PubMed:21861202]
Details
3. Bile salt export pump
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [PubMed:12739759]
  2. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on September 24, 2020 02:08

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