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外観
黄色～黄褐色, 粉末
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溶解性
ジメチルスルホキシドにやや溶けやすく、水、エタノール及びアセトンにほとんど溶けない。
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解説
C47H73NO17(924.08)．Streptomyces nodosusが産生するポリエン系抗生物質．黄色の柱または針状晶．分解点170 ℃．UV(メタノール)λmax 406，382，363，345 nm．[α]D24"－33.6°(0.1 mol L－1 メタノール塩酸)．アンホテリシンBは，真核細胞の細胞膜のステロールに結合して障害を与え，K＋ などを細胞内から放出させる．真菌のステロールであるエルゴステロールに，動物細胞膜のステロールであるコレステロールより親和性が強いために選択毒性を発揮する．副作用(発熱，悪心，おう吐など)は強いが，深在性真菌症治療薬として，おもに静脈注射で用いられる．LD50 4 mg/kg(マウス，静注)． 森北出版「化学辞典（第2版）
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用途
アムホテリシンB（アンフォテリシンB、アンポテリシンB、amphotericin B）とはポリエン系抗生物質の1つ。真菌の細胞膜のエルゴステロールと結合し、膜に小孔を作ることにより殺菌的に作用する。単体では黄色の結晶。
アスペルギルス属、カンジダ属、クリプトコッカス属を含む、幅広い真菌に対して効果を示す。腎毒性があるが、ナイスタチンよりは弱いため、全身性の真菌症には良い適応である。
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用途
ポリエン系抗菌剤です。細胞
膜と結合し、膜障害を起こすことにより、抗
菌作用を示します。
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効能
抗生物質, 抗真菌薬, 細胞膜機能阻害薬
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商品名
アムビゾーム (大日本住友製薬); ハリゾン (富士製薬工業); ハリゾン (富士製薬工業); ファンギゾン (ブリストル・マイヤーズスクイブ); ファンギゾン (ブリストル・マイヤーズスクイブ)
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化学的特性
Crystalline Yellow Solid
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使用
Amphotericin B is heptaene polyene antifungal originally discovered as a metabolite of Streptomyces nodosus in 1956. Amphotericin B acts by binding sterols in the cell membrane leading to the formation of transmembrane channels and subsequent ion leakage. Amphotericin B is poorly water soluble so has been developed for therapeutic use as a complex with desoxylate or in liposomes to improve bioavailability. Amphotericin B is widely used as a research reagent in diverse applications with over 15,000 literature citations.
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定義
ChEBI: Amphotericin B is a macrolide antibiotic used to treat potentially life-threatening fungal infections.
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適応症
Amphotericin B (Fungizone), a polyene antifungal drug
produced by the actinomycete Streptomyces nodosus,
consists of a large ring structure with both hydrophilic and lipophilic regions. Polyene antifungal drugs bind to
the fungal cell membrane component ergosterol, leading
to increased fungal cell membrane permeability and
the loss of intracellular constituents. Amphotericin has
a lesser affinity for the mammalian cell membrane component
cholesterol, but this interaction does account for
most adverse toxic effects associated with this drug.
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抗菌性
The spectrum includes most fungi that cause human disease:
A. fumigatus, Blast. dermatitidis, Candida spp., Coccidioides spp.,
Cryptococcus spp., Hist. capsulatum, Paracocc. brasiliensis and Spor.
schenckii. Dermatophytes, Fusarium spp. and some other Aspergillus
spp., including A. terreus and A. flavus, may be less susceptible,
while Scedosporium spp., Trichosporon asahii (formerly T. beigelii)
and some fungi that cause mucormycosis are resistant.
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獲得抵抗性
Resistant strains of C. tropicalis, C. lusitaniae, C. krusei and C.
guilliermondii, with alterations in the cell membrane, including
reduced amounts of ergosterol, have occasionally been isolated
after prolonged treatment, particularly of infections in
partially protected sites, such as the vegetations of endocarditis.
Significant resistance in yeasts, including C. albicans and
C. glabrata, has been reported in isolates from cancer patients
with prolonged neutropenia. In some cases resistant strains
have caused disseminated infection. There are a few reports of
amphotericin-resistant strains of Cryp. neoformans recovered
from AIDS patients with relapsed meningitis.
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危険性
May have undesirable side effects.
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応用例（製薬）
A fermentation product of Streptomyces nodosus available for
intravenous infusion or oral administration. The traditional
micellar suspension formulation is often associated with serious
toxic effects, in particular renal damage, and this has
stimulated efforts to develop chemical modifications and new
formulations.
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薬物動態学
Less than 10% of a parenteral dose of the conventional micellar
suspension of amphotericin B remains in the blood 12 h
after administration. The remainder is thought to bind to tissue
cell membranes, the highest concentrations being found
in the liver (up to 40% of the dose). Levels in the CSF are
less than 5% of the simultaneous blood concentration. The
conventional formulation has a terminal half-life of about 2
weeks. About 75% of a given dose is excreted unchanged in
the urine and feces. No metabolites have been identified.
The pharmacokinetics of lipid-based formulations are
quite diverse. Maximal serum concentrations of
the liposomal formulation are much higher than those of the
conventional micellar formulation, while levels of colloidal
dispersion and lipid complex formulations are lower due to
more rapid distribution of the drug to tissue. Administration
of lipid-associated formulations of amphotericin B results in
much higher drug concentrations in the liver and spleen than
are achieved with the conventional formulation. Renal concentrations
of the drug are much lower and its nephrotoxic
side effects are greatly reduced.
Blood concentrations are unchanged in hepatic or renal
failure. Hemodialysis does not influence serum concentrations
unless the patient is hyperlipidemic, in which case
there is some drug loss due to adherence to the dialysis
membrane.
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薬理学
This compound has a broad spectrum of antifungal activity, including Candida albicans,
Leishmania brasiliensis, Mycobacterium leprae, Histoplasma capsulatum, Blastomyces
dermatitidus, and Coccidioides immitis. It possesses fungistatic and fungicidal activity
depending on the dose used. The antifungal activity of amphotericin B is exhibited
because it binds with sterols, in particular with ergosterol in the cellular membrane of
sensitive fungi. This reaction makes pores in the membrane and increases the permeability of the membrane to small molecules, thus reducing the function of the membrane
as an osmotic barrier and making the cells more sensitive to being destroyed.
Amphotericin B is active against growing cells and cells that are dormant. However, this
compound is not highly selective and reacts with host mammalian cells. Despite the
many side effects, amphotericin B remains the primary drug for treating severe, acute
systemic fungal infections. It is used for generalized fungal infections, such as candidomycosis, aspergillosis, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis, and pulmonary mycoses. Synonyms of this drug are amphocyclin, fungisone,
fungilin, and others.
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臨床応用
Amphotericin B is most commonly used to treat serious
disseminated yeast and dimorphic fungal infections in
immunocompromised hospitalized patients. As additional
experience has been gained in the treatment of
fungal infections with the newer azoles, the use of amphotericin
B has diminished; if azole drugs have equivalent
efficacy, they are preferred to amphotericin B because
of their reduced toxicity profile and ease of
administration. For the unstable neutropenic patient
with Candida albicans fungemia, amphotericin B is the
drug of choice.
Amphotericin B remains the drug of choice in the
treatment of invasive aspergillosis, locally invasive mucormycosis,
and many disseminated fungal infections
occurring in immunocompromised hosts (the patient
population most at risk for serious fungal infections).
For example, the febrile neutropenic oncology patient
with persistent fever despite empirical antibacterial
therapy is best treated with amphotericin B for possible
Candida spp. sepsis.
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副作用
Common side effects of conventional amphotericin B include
hypotension, fever, rigors, chills, headache, backache, nausea,
vomiting, anorexia, anemia, disturbances in renal function
(including hypokalemia and hypomagnesemia), renal toxicity,
abnormal liver function (discontinue treatment), rash
and anaphylactoid reactions. Risk factors for nephrotoxicity
include average daily dose, concomitant treatment with other
nephrotoxic drugs and elevated baseline serum creatinine.
The lipid-associated formulations all lower the risk of
amphotericin B-induced renal failure. However, infusionrelated
side effects, such as fever, rigors and hypotension,
develop in up to 40% of patients treated with the colloidal
dispersion, and hypoxic events also occur; as a result
this formulation is not widely used. In contrast, infusionrelated
reactions are uncommon with liposomal amphotericin
B or the lipid complex. Patients who have developed
renal impairment while receiving the conventional formulation
of amphotericin B have improved or stabilized when
lipid-associated amphotericin B was substituted, even when
the dose was increased. Renal function should be measured
at regular intervals, particularly in patients receiving other
nephrotoxic drugs.
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安全性プロファイル
Poison by intravenous
and intraperitoneal routes. Human systemic
effects by intravenous route: leukopenia,
lung changes, and cardiac changes.Experimental reproductive effects. Mutation
data reported. When heated to
decomposition it emits toxic fumes of NOx.
