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Drug

D0073 | Ketoconazole

Molecular Formula C26H28Cl2N4O4
Molecular Weight 531.4
Structure
State solid
Protein binding 99% (in vitro, plasma protein binding)
Half life 2 hours
Absorption Moderate
Description a synthetic imidazole based antifungal drug; pan-inhibitor of the PXR nuclear receptor in xenobiotic metabolism (Cyp3A4) in vivo

G

J

D

J02AB02 Ketoconazole


[J02AB] Imidazole derivatives


[J02A] ANTIMYCOTICS FOR SYSTEMIC USE


[J02] ANTIMYCOTICS FOR SYSTEMIC USE


[J] Antiinfectives for systemic use

G01AF20 Combinations of imidazole derivatives


[G01AF] Imidazole derivatives


[G01A] ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS


[G01] GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS


[G] Genitourinary system and reproductive hormones

G01AF11 Ketoconazole


[G01AF] Imidazole derivatives


[G01A] ANTIINFECTIVES AND ANTISEPTICS, EXCL. COMBINATIONS WITH CORTICOSTEROIDS


[G01] GYNECOLOGICAL ANTIINFECTIVES AND ANTISEPTICS


[G] Genitourinary system and reproductive hormones

D01AC08 Ketoconazole


[D01AC] Imidazole and triazole derivatives


[D01A] ANTIFUNGALS FOR TOPICAL USE


[D01] ANTIFUNGALS FOR DERMATOLOGICAL USE


[D] Dermatological drugs

Toxicity Dose Time Species Model Method Action Positive criterion Reference
UNCOUPLING increase 36
MEMBRANE POTENTIAL 10.81±3.25 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 5.48 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL rat hepatocytes MMP assay Negative IC50 163
MEMBRANE POTENTIAL 243 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION 2.9 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
STATE 3 RESPIRATION I50=32, 74, 65, 75, 500μM for substrates Glutamate/Malate, Pyruvate/Malate, Ornithine/Malate, Arginine/Malate and Succinate repectively rat liver mitochondria Clark electrode inhibit 303
ELECTRON TRANSPORT CHAIN decrease 35
ELECTRON TRANSPORT CHAIN decrease 36
SWELLING > 400 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase inhibitor 35
NADH:ubiquinone reductase inhibitor 36
NADH:ubiquinone reductase > 400 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 40-100 μM rat liver mitochondria The reduction of ferricyanide by succinate cata-lyzed by SDH was monitored spectrophotometrically inhibitor 303
Succinate dehydrogenase 2.9 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Cytochrome c > 400 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]


H360F ***: May damage fertility [Danger Reproductive toxicity]


H373 **: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


 P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

Aggregated GHS information provided by 264 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H301 (99.24%): Toxic if swallowed [Danger Acute toxicity, oral]


H360 (99.24%): May damage fertility or the unborn child [Danger Reproductive toxicity]


H373 (98.86%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H400 (40.53%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


H410 (99.24%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]


H360F: May damage fertility [Danger Reproductive toxicity]


H373: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


 P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H301: Toxic if swallowed [Danger Acute toxicity, oral]


H360: May damage fertility or the unborn child [Danger Reproductive toxicity]


H373: Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]


H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]


 P201, P202, P260, P264, P270, P273, P281, P301+P310, P308+P313, P314, P321, P330, P391, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Blastomycosis

  • Body tinea

  • Candiduria

  • Chromoblastomycosis

  • Coccidioidomycosis

  • Dandruff

  • Fungal infection

  • Histoplasmosis

  • Infection

  • Meningitis fungal

  • Mucocutaneous candidiasis

  • Oral candidiasis

  • Paracoccidioides infection

  • Pityriasis

  • Skin candida

  • Tinea cruris

  • Tinea infection

  • Tinea pedis

  • Tinea versicolour

  • Application site burn

  • Application site pain

  • Application site reaction

    • 1-(4-(4-((2-((1H-Imidazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)ethanone 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 1-[4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]ethanone
    1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(imidazolylmethyl)(1,3-dioxolan-4-yl) ]methoxy}phenyl)piperazine
    1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1h-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]-methoxy] phenyl]piperazine 2-(2,4-Dichlorophenyl)-2-[(1H-imidazole-1-yl)methyl]-4-[[4-(4-acetyl-1-piperazinyl)phenoxy]methyl]-1,3-dioxolane 29521-EP2272972A1
    29521-EP2272973A1 29521-EP2277872A1 29521-EP2281816A1
    29521-EP2311842A2 65277-42-1 79156-75-5
    A19432 AKOS015918262 BDBM151585
    BRD-A76019558-001-01-0 CHEBI:48339 CHEMBL157101
    CTK5E6507 DB-054790 DB01026
    DTXSID20273956 Ethanone,1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-piperazinyl]- FT-0627575
    FT-0656627 GTPL2568 HMS3267K04
    KW 1414 Ketoconazol Ketoconazolum
    MCULE-7223272511 NCI60_002728 NSC-317629
    NSC317629 Nizoral Oprea1_683648
    Piperazine, (+/-)-1-acetyl-4-(4-(((2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-, rel- Q407883 R-41400
    SCHEMBL18258319 SCHEMBL8408 ST51039034
    STL481884 US8987315, Ketoconazole fungarest;fungoral
    ketoconazole

    DrugBank Name Ketoconazole
    DrugBank DB01026
    CAS Number 142128-57-2, 65277-42-1, 79156-75-5, 83374-59-8, 97073-69-3
    PubChem Compound 3823
    KEGG Drug D00351
    PubChem.Substance 46506746
    ChEBI 48339
    PharmGKB PA450146
    ChemSpider 3691
    BindingDB 151585.0
    TTD DAP000630
    Wikipedia Ketoconazole
    HET KTN
    DPD 1855

    1. Dykens et al. (2007)