作用機制: Amphotericin B is fungistatic or fungicidal depending on the concentration.
It works by binding to sterols—primarily **ergosterol**—in the fungal cell membrane. This binding creates transmembrane pores → alters membrane permeability → allows intracellular **potassium (K+)**, magnesium, and other vital cellular constituents to leak out → leading to fungal cell death.
*Toxicity Mechanism:* Mammalian cell membranes contain cholesterol. While amphotericin B has a higher affinity for ergosterol, it still binds to mammalian cholesterol to some degree. This cross-reactivity, particularly in renal epithelial cells, is the primary mechanism behind its dose-limiting nephrotoxicity. It also induces renal vasoconstriction, leading to a decreased glomerular filtration rate (GFR).
各物種劑量
Sheep
Susceptible systemic fungal infections (Llama) · 1 mg test dose, then initially at 0.3 mg/kg IV over 4 hours... Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1 mg/kg q48h IV for 6 weeks · IV · q48h · 6 weeks · Single case report in a Llama (Coccidioidomycosis).
Dogs
Susceptible systemic fungal infections (Rapid-Infusion Technique) · 0.25 mg/kg IV over 5 minutes, then 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given · IV · 3 times a week · Until 9-12 mg/kg accumulated · Dilute in 30 mL of 5% dextrose. Flush with 10 mL D5W before and after.
Susceptible systemic fungal infections (Slow IV Infusion Technique) · 0.25 mg/kg IV over 4-6 hours, then 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given · IV · 3 times a week · Until 9-12 mg/kg accumulated · Dilute in 250-500 mL of D5W.
Systemic fungal infections (Dehydrated/compromised) · 0.5 mg/kg diluted in D5W given by slow IV over 15 minutes (normal renal) or 3-6 hours (compromised renal) · IV · Every other day · Until cumulative dose of 8-10 mg/kg (or higher depending on disease) · Must rehydrate before administration. Discontinue if BUN exceeds 50 mg/dL.
Systemic mycoses (Lipid-based: AmBisome, Amphocil, Abelcet) · Test dose of 0.5 mg/kg; then 1-2.5 mg/kg IV q48h (or Monday, Wednesday, Friday) for 4 weeks or until the total cumulative dose is reached · IV · q48h · 4 weeks or until cumulative dose reached · 1 mg/kg for susceptible yeast/dimorphic fungi (cumulative 12 mg/kg); 2-2.5 mg/kg for resistant filamentous fungi (cumulative 24-30 mg/kg).
Systemic mycoses (ABLC; Abelcet) · 2-3 mg/kg IV three days per week for a total of 9-12 treatments (cumulative dose of 24-27 mg) · IV · 3 days per week · 9-12 treatments · Dilute to 1 mg/mL in D5W and infuse over 1-2 hours.
給藥途徑
IVSCIntratrachealNebulizationIntrauterinePO (Birds only for specific GI infections)Topical
禁忌症
Patients with known hypersensitivity to amphotericin B (unless the infection is life-threatening and no alternatives exist)
不良反應
Nephrotoxicity (very common, dose-dependent)
Anorexia and vomiting
Hypokalemia and hypomagnesemia
Distal renal tubular acidosis
Phlebitis at injection site
Cardiac arrhythmias
Non-regenerative anemia
Fever (can be mitigated with NSAIDs or low-dose steroids)
Fluorouracil · Amphotericin may increase the toxic effects of fluorouracil. · major
Doxorubicin · Amphotericin may increase the toxic effects of doxorubicin. · major
Methotrexate · Amphotericin may increase the toxic effects of methotrexate. · major
Nephrotoxic drugs · Concurrent use significantly increases the risk of severe nephrotoxicity. · major
監測
BUN and serum creatinine (before each dose or every other day during dose escalation, then at least weekly)
Serum electrolytes including sodium, potassium, and magnesium (weekly)
Liver function tests (weekly)
CBC and Packed Cell Volume (PCV) (weekly)
Urinalysis (weekly)
Total plasma protein (TPP) (at least weekly)
Body weight
過量
Acute intravenous overdose reports are rare. Because of the severe toxicity of the drug, dosage calculations and solution preparation procedures must be double-checked.
If an accidental overdose occurs, **renal toxicity** is the primary concern. Toxicity may be minimized by aggressively administering **intravenous fluids** and **mannitol** to maintain GFR and promote diuresis.
Blastomycosis · 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given · IV · 3 times weekly · Until 6 mg/kg cumulative · Given with ketoconazole.
Blastomycosis · 0.15-0.5 mg/kg IV 3 times a week · IV · 3 times a week · Until total dose reaches 4-6 mg/kg, then start maintenance · Given with ketoconazole.
Blastomycosis (severe cases, using Abelcet) · 1-2 mg/kg IV three times a week (or every other day) to a cumulative dose of 12-24 mg/kg · IV · 3 times a week · Until 12-24 mg/kg cumulative
Cryptococcosis · 0.5-0.8 mg/kg SC 2-3 times per week · SC · 2-3 times per week · Diluted in 0.45% NaCl with 2.5% dextrose. Concentrations >20 mg/L result in local irritation/sterile abscess.
Histoplasmosis · 0.15-0.5 mg/kg IV 3 times a week · IV · 3 times a week · Until total dose reaches 2-4 mg/kg, then start maintenance · Given with ketoconazole.
Histoplasmosis · 0.5 mg/kg IV given over 6-8 hours. If dose is tolerated, increase to 1 mg/kg given on alternate days until total dose of 7.5-8.5 mg/kg cumulative dose is achieved · IV · Alternate days · Until 7.5-8.5 mg/kg cumulative · Alternative to ketoconazole treatment.
Leishmaniasis (Liposomal form) · 3-3.3 mg/kg IV 3 times weekly for 3-5 treatments · IV · 3 times weekly · 3-5 treatments
Leishmaniasis (AmBisome) · Give initial test dose of 0.5 mg/kg, then 3-3.3 mg/kg IV every 72-96 hours until a cumulative dose of 15 mg/kg is reached · IV · q72-96h · Until 15 mg/kg cumulative
Gastrointestinal pythiosis (ABLC; Abelcet) · 1-2 mg/kg IV three times weekly for 4 weeks (cumulative dose 12-24 mg) · IV · 3 times weekly · 4 weeks · Follow-up medical therapy after surgical resection.
Systemic fungal infections and leishmaniosis · Dose not specified in monograph; requires specific protocols · IV · As directed · Until clinical resolution · Lipid formulations preferred if pre-existing renal insufficiency exists.
Birds
Aspergillosis (raptors and psittacines) · 1.5 mg/kg IV three times daily for 3 days · IV · q8h · 3 days · With or followed by flucytosine.
Aspergillosis (raptors and psittacines) · 1 mg/kg diluted in sterile water once to 3 times daily for 3 days · Intratracheal · q8-24h · 3 days · In conjunction with flucytosine.
Aspergillosis · 1.5 mg/kg IV q12h for 3-5 days; topically in the trachea at 1 mg/kg q12h; 0.3-1 mg/mL nebulized for 15 minutes 2-4 times daily · IV/Intratracheal/Nebulization · Variable · 3-5 days (IV)
Macrorhabdiasis (Microrhabdus ornithogaster) · 100-150 mg/kg PO q12h for 30 days · PO · q12h · 30 days · Treatment failures common with shorter durations.
Cats
Susceptible systemic fungal infections (Rapid-Infusion Technique) · 0.25 mg/kg IV over 5 minutes 3 times a week until 9-12 mg/kg accumulated dosage is given · IV · 3 times a week · Until 9-12 mg/kg accumulated · Dilute in 30 mL of 5% dextrose. Flush with 10 mL D5W before and after.
Cryptococcosis · 0.25 mg/kg in 30 mL D5W IV over 15 minutes q48h · IV · q48h · 3-4 weeks after clinical signs resolve · Given with flucytosine. Stop if BUN >50 mg/dL.
Cryptococcosis · 0.15-0.4 mg/kg IV 3 times a week · IV · 3 times a week · Until total dose reaches 4-6 mg/kg, then start maintenance · Given with flucytosine.
Cryptococcosis · 0.5-0.8 mg/kg SC 2-3 times per week · SC · 2-3 times per week · Diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats).
Cryptococcosis (ABLC; Abelcet) · 1 mg/kg IV three days per week for a total of 12 treatments (cumulative dose of 12 mg) · IV · 3 days per week · 12 treatments · Dilute to 1 mg/mL in D5W and infuse over 1-2 hours.
Histoplasmosis · 0.25 mg/kg in 30 mL D5W IV over 15 minutes q48h · IV · q48h · 4-8 weeks · Given with ketoconazole. Stop if BUN >50 mg/dL.
Histoplasmosis · 0.15-0.5 mg/kg IV 3 times a week · IV · 3 times a week · Until total dose reaches 2-4 mg/kg, then start maintenance · Given with ketoconazole.
Blastomycosis · 0.25 mg/kg in 30 mL D5W IV over 15 minutes q48h · IV · q48h · Until cumulative dose of 4 mg/kg is given · Given with ketoconazole. Stop if BUN >50 mg/dL.
Blastomycosis · 0.15-0.5 mg/kg IV 3 times a week · IV · 3 times a week · Until total dose reaches 4-6 mg/kg, then start maintenance · Given with ketoconazole.
Systemic fungal infections (e.g., cryptococcosis) · Dose not specified in monograph; requires specific protocols · IV · As directed · Until clinical resolution · SC alternative has been used for cryptococcosis if regular venous catheterization is problematic.
Cryptococcosis (when IV access is problematic) · Dose not specified in monograph; requires specific protocols · SC · As directed · Until clinical resolution · SC route used as an alternative to IV.
Horses
Fungal pneumonia · Day 1: 0.3 mg/kg IV; Day 2: 0.4 mg/kg IV; Day 3: 0.6 mg/kg IV; days 4-7: no treatment; then every other day until a total cumulative dose of 6.75 mg/kg has been administered · IV · Variable · Until 6.75 mg/kg cumulative
Phycomycoses and pulmonary mycoses · Day 1: 0.3 mg/kg IV; Day 2: 0.45 mg/kg IV; Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) · IV · Variable · 10-80 days · Administer in 1L D5W at 1 L/hr. Adjust if toxicity occurs.
Intrauterine infusion · 200-250 mg · Intrauterine · q24h or q48h · 3-7 days · Little science available for recommending doses/diluents.
SmallMammals
Susceptible systemic fungal infections (Rabbits) · 1 mg/kg/day IV · IV · q24h
Reptiles
Susceptible fungal respiratory infections · 1 mg/kg diluted in saline and given intra-tracheally once daily for 14-28 treatments · Intratracheal · q24h · 14-28 treatments