Peringatan Keamanan

Symptoms of overdose include acute liver injury, which may include both hepatocellular and cholestatic injury, accompanied by anorexia, fatigue, nausea, and jaundice.L10292,A188048 In case of overdose, gastric lavage with activated charcoal may be used if within one hour of ketoconazole ingestion otherwise provide supportive care.FDA Label,L7736 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.L7736

Ketoconazole

DB01026

small molecule approved investigational

Deskripsi

Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.FDA Label It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.A181802,T116 Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981.A188054 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.A188054,A188057 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.

Struktur Molekul 2D

Berat 531.431
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (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.[A181802]
Volume Distribusi Ketoconazole has an estimated volume of distribution of 25.41 L or 0.36 L/kg.[A181802] It distributes widely among the tissues, reaching effective concentrations in the skin, tendons, tears, and saliva.[A181805] 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.[A181802]
Klirens (Clearance) Ketoconazole has an estimated clearance of 8.66 L/h.[A181802]

Absorpsi

Ketoconazole requires an acidic environment to become soluble in water.A181805 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.A181802,L7739 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.A181802,A181805 A bioavailablity of 76% has been reported for ketoconazole.A181802

Metabolisme

The major metabolite of ketoconazole appears to be M2, an end product resulting from oxidation of the imidazole moiety.A181868 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.

Rute Eliminasi

Only 2-4% of the ketoconazole dose is eliminated unchanged in the urine.A181802 Over 95% is eliminated through hepatic metabolism.

Interaksi Makanan

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

Interaksi Obat

1479 Data
Afatinib The serum concentration of Afatinib can be increased when it is combined with Ketoconazole.
Cyclosporine Ketoconazole may increase the nephrotoxic activities of Cyclosporine.
Bosutinib The serum concentration of Bosutinib can be increased when it is combined with Ketoconazole.
Brentuximab vedotin The serum concentration of Brentuximab vedotin can be increased when it is combined with Ketoconazole.
Glycochenodeoxycholic Acid Ketoconazole may decrease the excretion rate of Glycochenodeoxycholic Acid which could result in a higher serum level.
Glimepiride Ketoconazole may decrease the excretion rate of Glimepiride which could result in a higher serum level.
Olmesartan Olmesartan may decrease the excretion rate of Ketoconazole which could result in a higher serum level.
Spironolactone The risk or severity of hyperkalemia can be increased when Ketoconazole is combined with Spironolactone.
Atropine Ketoconazole may decrease the excretion rate of Atropine which could result in a higher serum level.
Fluorescein Ketoconazole may decrease the excretion rate of Fluorescein which could result in a higher serum level.
Nitrofurantoin Ketoconazole may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Cefaclor Ketoconazole may decrease the excretion rate of Cefaclor which could result in a higher serum level.
Telmisartan Ketoconazole may decrease the excretion rate of Telmisartan which could result in a higher serum level.
Dipyridamole Ketoconazole may decrease the excretion rate of Dipyridamole which could result in a higher serum level.
Sulfamethoxazole Ketoconazole may decrease the excretion rate of Sulfamethoxazole which could result in a higher serum level.
Ofloxacin Ketoconazole may decrease the excretion rate of Ofloxacin which could result in a higher serum level.
Taurocholic acid Ketoconazole may decrease the excretion rate of Taurocholic acid which could result in a higher serum level.
Pitavastatin The metabolism of Pitavastatin can be decreased when combined with Ketoconazole.
Indocyanine green acid form Ketoconazole may decrease the excretion rate of Indocyanine green acid form which could result in a higher serum level.
Benzbromarone Ketoconazole may decrease the excretion rate of Benzbromarone which could result in a higher serum level.
Pilsicainide Ketoconazole may decrease the excretion rate of Pilsicainide which could result in a higher serum level.
Glycyrrhizic acid Ketoconazole may decrease the excretion rate of Glycyrrhizic acid which could result in a higher serum level.
Flucloxacillin Ketoconazole may decrease the excretion rate of Flucloxacillin which could result in a higher serum level.
Glipizide Ketoconazole may decrease the excretion rate of Glipizide which could result in a higher serum level.
Belantamab mafodotin Ketoconazole may decrease the excretion rate of Belantamab mafodotin which could result in a higher serum level.
Edoxaban The serum concentration of Edoxaban can be increased when it is combined with Ketoconazole.
Ledipasvir The serum concentration of Ledipasvir can be increased when it is combined with Ketoconazole.
Naloxegol The serum concentration of Naloxegol can be increased when it is combined with Ketoconazole.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Ketoconazole.
Prucalopride The serum concentration of Prucalopride can be increased when it is combined with Ketoconazole.
Silodosin The excretion of Silodosin can be decreased when combined with Ketoconazole.
Topotecan The serum concentration of Topotecan can be increased when it is combined with Ketoconazole.
Cilostazol The serum concentration of Cilostazol can be increased when it is combined with Ketoconazole.
Amphotericin B The therapeutic efficacy of Amphotericin B can be decreased when used in combination with Ketoconazole.
Didanosine Didanosine can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Eliglustat The metabolism of Eliglustat can be decreased when combined with Ketoconazole.
Ibrutinib The metabolism of Ibrutinib can be decreased when combined with Ketoconazole.
Everolimus The serum concentration of Everolimus can be increased when it is combined with Ketoconazole.
Rifaximin The serum concentration of Rifaximin can be increased when it is combined with Ketoconazole.
Sildenafil The serum concentration of Sildenafil can be increased when it is combined with Ketoconazole.
Colchicine The serum concentration of Colchicine can be increased when it is combined with Ketoconazole.
Fentanyl The metabolism of Fentanyl can be decreased when combined with Ketoconazole.
Iloperidone The metabolism of Iloperidone can be decreased when combined with Ketoconazole.
Retapamulin The metabolism of Retapamulin can be decreased when combined with Ketoconazole.
Tofacitinib The metabolism of Tofacitinib can be decreased when combined with Ketoconazole.
Zolmitriptan The metabolism of Zolmitriptan can be decreased when combined with Ketoconazole.
Atomoxetine The metabolism of Atomoxetine can be decreased when combined with Ketoconazole.
R,S-Warfarin alcohol The serum concentration of R,S-Warfarin alcohol can be increased when it is combined with Ketoconazole.
S,R-Warfarin alcohol The serum concentration of S,R-Warfarin alcohol can be increased when it is combined with Ketoconazole.
Midazolam The serum concentration of Midazolam can be increased when it is combined with Ketoconazole.
Agomelatine The serum concentration of Agomelatine can be increased when it is combined with Ketoconazole.
Pirfenidone The metabolism of Pirfenidone can be decreased when combined with Ketoconazole.
Tizanidine The serum concentration of Tizanidine can be increased when it is combined with Ketoconazole.
Tacrolimus The serum concentration of Tacrolimus can be increased when it is combined with Ketoconazole.
Aliskiren The serum concentration of Aliskiren can be increased when it is combined with Ketoconazole.
Atorvastatin The serum concentration of Atorvastatin can be increased when it is combined with Ketoconazole.
Boceprevir The serum concentration of Boceprevir can be increased when it is combined with Ketoconazole.
Carbocisteine The risk or severity of adverse effects can be increased when Ketoconazole is combined with Carbocisteine.
Cobicistat The serum concentration of Cobicistat can be increased when it is combined with Ketoconazole.
Dabigatran etexilate The serum concentration of Dabigatran etexilate can be increased when it is combined with Ketoconazole.
Darunavir The serum concentration of Darunavir can be increased when it is combined with Ketoconazole.
Elvitegravir The serum concentration of Elvitegravir can be increased when it is combined with Ketoconazole.
Fexofenadine The serum concentration of Fexofenadine can be increased when it is combined with Ketoconazole.
Fingolimod The serum concentration of Fingolimod can be increased when it is combined with Ketoconazole.
Amprenavir The serum concentration of Ketoconazole can be increased when it is combined with Amprenavir.
Fosamprenavir The serum concentration of Ketoconazole can be increased when it is combined with Fosamprenavir.
Isoniazid The serum concentration of Ketoconazole can be decreased when it is combined with Isoniazid.
Lopinavir The serum concentration of Lopinavir can be increased when it is combined with Ketoconazole.
Mirabegron The serum concentration of Mirabegron can be increased when it is combined with Ketoconazole.
Ritonavir The bioavailability of Ketoconazole can be increased when combined with Ritonavir.
Saquinavir The serum concentration of Ketoconazole can be increased when it is combined with Saquinavir.
Tadalafil The serum concentration of Tadalafil can be increased when it is combined with Ketoconazole.
Telaprevir The serum concentration of Telaprevir can be increased when it is combined with Ketoconazole.
Sirolimus The serum concentration of the active metabolites of Sirolimus can be increased when Sirolimus is used in combination with Ketoconazole.
Temsirolimus The serum concentration of the active metabolites of Temsirolimus can be increased when Temsirolimus is used in combination with Ketoconazole.
Eluxadoline The serum concentration of Eluxadoline can be increased when it is combined with Ketoconazole.
Vincristine The excretion of Vincristine can be decreased when combined with Ketoconazole.
Doxorubicin The serum concentration of Doxorubicin can be increased when it is combined with Ketoconazole.
Magnesium oxide Magnesium oxide can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sodium bicarbonate Sodium bicarbonate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxide Aluminum hydroxide can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium carbonate Calcium carbonate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magaldrate Magaldrate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium hydroxide Magnesium hydroxide can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium trisilicate Magnesium trisilicate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium carbonate Magnesium carbonate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Bismuth subnitrate Bismuth subnitrate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium silicate Magnesium silicate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium acetoacetate Aluminium acetoacetate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Hydrotalcite Hydrotalcite can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium peroxide Magnesium peroxide can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Almasilate Almasilate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium glycinate Aluminium glycinate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aloglutamol Aloglutamol can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Calcium silicate Calcium silicate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphate Aluminium phosphate can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Dexrabeprazole Dexrabeprazole can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Pantoprazole Pantoprazole can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Omeprazole Omeprazole can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.
Lansoprazole Lansoprazole can cause a decrease in the absorption of Ketoconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.

Target Protein

Lanosterol 14-alpha demethylase ERG11
Lanosterol 14-alpha demethylase ERG11
Steroid 17-alpha-hydroxylase/17,20 lyase CYP17A1
Androgen receptor AR
Steroid 21-hydroxylase CYP21A2
Voltage-gated inwardly rectifying potassium channel KCNH2 KCNH2
Nuclear receptor subfamily 1 group I member 2 NR1I2
Nuclear receptor subfamily 1 group I member 3 NR1I3

Referensi & Sumber

Synthesis reference: U.S. Patent 4,144,346.
Artikel (PubMed)
  • PMID: 10933341
    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.
  • PMID: 10451809
    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.
  • PMID: 15737124
    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.
  • PMID: 12476017
    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.
  • PMID: 6151171
    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.
  • PMID: 3280211
    Daneshmend TK, Warnock DW: Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet. 1988 Jan;14(1):13-34. doi: 10.2165/00003088-198814010-00002.
  • PMID: 14675275
    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.
  • PMID: 19799546
    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.
Menampilkan 8 dari 10 artikel.
Textbook
  • ISBN: 978-1-25-958473-2
    Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.

Contoh Produk & Brand

Produk: 173 • International brands: 10
Produk
  • Apo-ketoconazole
    Tablet • 200 mg • Oral • Canada • Generic • Approved
  • Danil
    Solution • 15 mg/100mL • Topical • US • OTC
  • Danil
    Solution • - • Topical • US • OTC
  • Danil
    Solution • - • Topical • US • OTC
  • Dermetazole
    Cream; Kit • - • Topical • US
  • Extina
    Aerosol, foam • 20 mg/1g • Topical • US • Approved
  • Extina
    Aerosol, foam • 20 mg/1g • Topical • US • Approved
  • Extina
    Aerosol, foam • 20 mg/1g • Topical • US • Approved
Menampilkan 8 dari 173 produk.
International 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

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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