์์ฉ ๊ธฐ์ : **Antifungal Action:**
Ketoconazole inhibits **lanosterol 14ฮฑ-demethylase**, a fungal **cytochrome P450** enzyme โ blocks the conversion of lanosterol to **ergosterol** โ depletion of ergosterol in the fungal cell membrane โ accumulation of toxic intermediate sterols โ increased cellular membrane permeability and cell death. It is primarily fungistatic but can be fungicidal at high concentrations or prolonged exposures.
**Endocrine/Metabolic Action:**
It reversibly inhibits mammalian **cytochrome P450** enzymes (specifically **CYP11A1** and **CYP17**) โ blocks the synthesis of adrenal and gonadal steroids โ decreases **cortisol** and **testosterone** production.
**Immunomodulatory Action:**
Inhibits **5-lipooxygenase**, providing mild anti-inflammatory effects, and suppresses T-lymphocyte proliferation.
๋๋ฌผ ์ข ๋ณ ์ฉ๋
Cats
Coccidioidomycosis ยท 10-30 mg/kg PO divided twice a day ยท PO ยท q12h ยท 6-12 months ยท Use in cats is controversial
Coccidioidomycosis ยท 50 mg per cat PO once daily; or 25-75 mg per cat q12-48h ยท PO ยท q24h or q12-48h ยท 9-12 months on average
Blastomycosis ยท 10 mg/kg q12h PO ยท PO ยท q12h ยท At least 60 days ยท Used with amphotericin B
Cryptococcosis ยท 10 mg/kg twice daily ยท PO ยท q12h ยท Can produce anorexia and debility at this dosage
Aspergillosis ยท 10 mg/kg PO q12h ยท PO ยท q12h
Dermatophytosis ยท 10 mg/kg PO once daily with an acidic meal ยท PO ยท q24h ยท Prolonged; 2 weeks beyond clinical cure and negative cultures ยท Reserved for when griseofulvin ineffective or not tolerated
Sporotrichosis ยท 5-10 mg/kg PO q12-24h ยท PO ยท q12-24h ยท 2-4 months on average
Horses
Susceptible yeasts and Aspergillus spp ยท 5 mg/kg PO once daily ยท PO ยท q24h ยท Using commercial oral solution
Scopulariopsis pneumonia ยท 30 mg/kg q12h ยท NG tube ยท q12h ยท Administered via NG tube mixed with 0.2 Normal hydrochloric acid
Birds
Severe refractory candidiasis in Psittacines ยท 5-10 mg/kg as a gavage twice daily ยท PO (gavage) ยท q12h ยท 14 days ยท Dissolve in 0.2 mL 1 N HCl and add 0.8 mL water
ํฌ์ฌ ๊ฒฝ๋ก
POTopical
๊ธ๊ธฐ
Known hypersensitivity to ketoconazole
Controversial/Contraindicated in cats (due to toxicity risks)
Concurrent use with cisapride or ivermectin (in dogs)
Transient suppression of gonadal and adrenal steroid synthesis
Infertility in male dogs (reversible)
Hepatotoxicity
Anorexia
Alterations in hair-coat colour
Thrombocytopenia (at high doses)
Adrenal insufficiency (at high doses)
Cataract development (in dogs)
Teratogenic effects
์ฝ๋ฌผ ์ํธ์์ฉ
Alcohol ยท May produce a disulfiram-like reaction (vomiting)
Antacids ยท May reduce oral absorption of ketoconazole; administer at least 1 hour before or 2 hours after ยท moderate
Tricyclic Antidepressants (amitriptyline, clomipramine) ยท Ketoconazole may reduce metabolism and increase adverse effects
Benzodiazepines (midazolam, triazolam) ยท Ketoconazole may increase levels
Buspirone ยท Plasma concentrations may be elevated
Busulfan ยท Ketoconazole may increase levels
Calcium-channel blockers (amlodipine, verapamil) ยท Ketoconazole may increase levels
Cisapride ยท Ketoconazole may increase cisapride levels and possibility for toxicity; use together contraindicated
Corticosteroids ยท Ketoconazole may inhibit metabolism; potential for increased adverse effects
Cyclophosphamide ยท Ketoconazole may inhibit metabolism; potential for increased toxicity
Cyclosporine ยท Increased cyclosporine levels (often used therapeutically to reduce cyclosporine dose)
Digoxin ยท Ketoconazole may increase digoxin levels
Fentanyl/Alfentanil ยท Ketoconazole may increase fentanyl or alfentanil levels
๋ชจ๋ํฐ๋ง
Liver enzymes with chronic therapy (at least every 1-2 months)
CBC with platelets
Clinical efficacy
Adverse effects (GI signs, jaundice)
Liver function tests (routine monitoring recommended)
Platelet count (if high doses are used)
Adrenal function/clinical signs of hypoadrenocorticism
๊ณผ์ฉ๋
No reports of acute toxicity associated with overdosage were located. The oral LD50 in dogs is >500 mg/kg. In the event of an acute overdose, employ supportive measures, including **gastric lavage with sodium bicarbonate**.
Susceptible fungal infections (most species) ยท 200 mg/L ยท PO (water) ยท Continuous ยท 7-14 days ยท Dissolve in acid prior to adding to water
Susceptible fungal infections (most species) ยท 10-20 mg/kg ยท PO (feed) ยท Daily ยท 7-14 days ยท Add to favorite food or mash
Susceptible fungal infections (Moluccan Cockatoos) ยท 20-30 mg/kg PO twice daily ยท PO ยท q12h
Susceptible fungal infections (Ratites) ยท 5-10 mg/kg PO once daily ยท PO ยท q24h
SmallMammals
Susceptible infections (Rabbits) ยท 10-40 mg/kg per day PO ยท PO ยท q24h ยท 14 days
Systemic mycoses/candidiasis (Hamsters, Gerbils, Mice, Rats, Guinea pigs, Chinchillas) ยท 10-40 mg/kg per day PO ยท PO ยท q24h ยท 14 days
Dogs
Coccidioidomycosis (systemic form) ยท 5-10 mg/kg PO twice daily ยท PO ยท q12h ยท Minimum of 3-6 months
Coccidioidomycosis (CNS form) ยท 15-20 mg/kg PO twice daily ยท PO ยท q12h ยท Minimum of 3-6 months
Coccidioidomycosis (bony lesions or relapses) ยท 5 mg/kg PO every other day ยท PO ยท q48h ยท Lifelong
Coccidioidomycosis ยท 10-30 mg/kg PO divided twice a day ยท PO ยท q12h ยท 6-12 months
Blastomycosis ยท 10 mg/kg PO twice daily (15-20 mg/kg PO twice daily if CNS involvement) ยท PO ยท q12h ยท At least 3 months ยท Used with amphotericin B
Blastomycosis ยท 20 mg/kg/day PO once daily or divided twice daily; 40 mg/kg divided twice daily for ocular or CNS involvement ยท PO ยท q24h or q12h ยท At least 2-3 months or until remission ยท Used with amphotericin B
Histoplasmosis ยท 10 mg/kg PO once a day or twice a day ยท PO ยท q24h or q12h ยท At least 3 months ยท Treat at least 30 days after complete resolution. Maintenance 5 mg/kg PO every other day indefinitely if relapse.
Histoplasmosis ยท 10-20 mg/day PO once daily or divided twice daily ยท PO ยท q24h or q12h ยท At least 2-3 months or until remission ยท Used with amphotericin B
Aspergillosis ยท 20 mg/kg PO ยท PO ยท Not specified ยท At least 6 weeks ยท May require long-term/maintenance therapy
Nasal aspergillosis ยท 10 mg/kg PO once daily (q24h) or 5 mg/kg PO q12h ยท PO ยท q24h or q12h ยท Many weeks; continue 1 month beyond last detection ยท Itraconazole somewhat more effective
Cryptococcosis ยท 10 mg/kg PO once daily or divided twice daily ยท PO ยท q24h or q12h ยท Maintenance ยท Used with amphotericin B
Fungal myocarditis ยท 10 mg/kg PO three times daily ยท PO ยท q8h
Candidiasis ยท 10 mg/kg PO once daily (q24h) or 5 mg/kg PO q12h ยท PO ยท q24h or q12h ยท Many weeks; continue 1 month beyond last detection
Sporotrichosis ยท 15 mg/kg PO q12h ยท PO ยท q12h ยท Many weeks; continue 1 month beyond last detection
Malassezia dermatitis (severe) ยท 5 mg/kg PO once daily to 10 mg/kg twice daily ยท PO ยท q24h to q12h ยท Until clinical signs abate and no organisms seen
Malassezia dermatitis ยท 5-10 mg/kg PO twice a day ยท PO ยท q12h ยท 30 days ยท Often used with therapeutic shampoos
Malassezia dermatitis ยท 5-10 mg/kg PO daily for 10 days, then every other day for an additional 10 days ยท PO ยท q24h then q48h ยท 20 days
Malassezia dermatitis ยท 5 mg/kg twice daily for 21-30 days, may increase to 10 mg/kg PO twice daily if poor response ยท PO ยท q12h ยท 21-30 days
Malassezia dermatitis ยท 2.5-10 mg/kg PO once daily (q24h) for 7-14 days; once a good response is seen taper to every other day (q48h) ยท PO ยท q24h then q48h ยท Until complete remission
Hyperadrenocorticism ยท 5-10 mg/kg PO twice daily initially; may increase to 15 mg/kg PO twice daily ยท PO ยท q12h ยท Long-term ยท Monitor with ACTH stimulation test
Hyperadrenocorticism ยท 5 mg/kg q12h for 5-7 days, increase to 10 mg/kg q12h for 10-14 days; many require 15-20 mg/kg q12h ยท PO ยท q12h ยท Long-term
Hyperadrenocorticism (palliative) ยท 15 mg/kg PO q12h ยท PO ยท q12h ยท Long-term
Reduce cyclosporine dosage ยท 5-10 mg/kg PO per day ยท PO ยท q24h ยท Concurrent with cyclosporine
Perianal fistula (with cyclosporine) ยท 7.5 mg/kg PO twice daily ยท PO ยท q12h ยท Given with cyclosporine 0.5-0.75 mg PO twice daily
Atopic dermatitis (with cyclosporine) ยท 5 mg/kg/day ยท PO ยท q24h ยท Given with cyclosporine 2.5 mg/kg/day
IMHA (with cyclosporine) ยท 10 mg/kg/day ยท PO ยท q24h ยท Allows reduction of cyclosporine dose
Reptiles
Susceptible infections (most species) ยท 15-30 mg/kg PO once daily ยท PO ยท q24h ยท 2-4 weeks
Fungal shell diseases in turtles/tortoises ยท 25 mg/kg PO once a day ยท PO ยท q24h ยท 2-4 weeks