암포테리신 B

항진균제 (폴리엔 마크로라이드)

**암포테리신 B(Amphotericin B)**는 진행성이며 치명적일 수 있는 진균 감염(예: 분아균증, 히스토플라스마증, 크립토코쿠스증, 콕시디오이데스증)에 사용되는 강력한 전신성 폴리엔 마크로라이드계 항진균제입니다. 경구 생체이용률이 낮아 반드시 비경구(일반적으로 IV)로 투여해야 합니다. 기존 형태인 **데옥시콜산 암포테리신 B**는 심각한 **신독성**을 유발하는 것으로 악명이 높으며, 이로 인해 사용이 제한되고 집중적인 모니터링이 필요합니다. 새로운 **지질 기반 제제**(예: 리포솜 암포테리신 B, 암포테리신 B 지질 복합체)는 약물을 지질 운반체에 캡슐화한 것입니다. 이러한 제제는 신독성이 현저히 낮고 더 높은 누적 용량을 허용하며 조직(폐, 간, 비장 등) 침투력이 더 좋지만 비용이 상당히 비쌉니다. *임상 팁:* 많은 이형성 진균에 매우 효과적이지만, 개와 고양이의 아스페르길루스증은 암포테리신 B 치료에 만족스럽게 반응하지 않는 경우가 많습니다.

작용 기전: 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).

동물 종별 용량

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.

투여 경로

IVSCIntratrachealNebulizationIntrauterinePO (Birds only for specific GI infections)Topical

금기

Patients with known hypersensitivity to amphotericin B (unless the infection is life-threatening and no alternatives exist)

이상반응

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)
Tachycardia, tachypnea, lethargy, restlessness (horses)
Calcinosis cutis (dogs)

약물 상호작용

Corticosteroids · May exacerbate the potassium-losing effects of amphotericin B.
Digoxin · Amphotericin B-induced hypokalemia may exacerbate digoxin toxicity.
Flucytosine · In vitro synergy against Cryptococcus and Candida, but may also increase flucytosine toxicity. · minor
Nephrotoxic Drugs (Aminoglycosides, Polymyxin B, Cisplatin, Cyclosporine, etc.) · Additive renal toxicity; avoid concurrent or sequential use if possible.
Potassium-Depleting Drugs (Thiazide or Loop Diuretics) · Increased risk of severe hypokalemia.
Saline Solutions or Preservative-containing Solutions · Reconstituting amphotericin B deoxycholate with these solutions may cause precipitation.
Skeletal Muscle Relaxants (Tubocurarine) · Amphotericin B-induced hypokalemia may enhance curariform effects.
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

모니터링

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

과용량

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.

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