アニデュラフンギン 化学特性,用途語,生産方法
効能
抗真菌薬, 細胞壁合成阻害薬
説明
Anidulafungin, a semi-synthetic derivative of echinocandin B, has been developed
and launched as an intravenous treatment for serious fungal infections,
such as candidemia, Candida-derived peritonitis, intra-abdominal abscesses, and
esophageal candidiasis. As a non-competitive inhibitor of 1,3-b-D-glucan synthase,
which is responsible for the formation of glucan polymers, anidulafungin
interferes with the cell wall synthesis of most pathogenic fungi. This mode of
action is characteristic of the echinocandin class of antifungals. While the first
member of this class, cilofungin, was withdrawn due to toxicity associated with
the formulation vehicle, anidulafungin follows the successful introduction
of caspofungin and micafungin.
Compared to the other echinocandins,
anidulafungin appears to be more potent (MIC90 ofr0.25 mg/mL for C.albicans,
0.5 mg/mL for C.glabrata, 1 mg/mL for C. krusel and C.tropicalis, 2mg/mL for
C.lusitaniae, and 2 mg/mL for Aspergillus spp) and is devoid of significant drug
interactions since it is neither an inhibitor nor substrate of the cytochrome P450
isoenzymes. The emergence of the echinocandins circumvents the concern
regarding the rising resistance to the azole and amphotericin B antifungals; no
cross-resistance is expected because the echinocandins work at the cell wall
rather than the cell membrane.
使用
Anidulafungin is a semi-synthetic cyclic lipopeptide belonging to the echinocandin class that was reported in 1995 and commercially developed by Eli Lilly. Anidulafungin inhibits the synthesis of β-(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi and is extensively referenced in the literature with over 400 citations.
定義
ChEBI: A semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis.
抗菌性
It is active against Aspergillus spp., Candida spp. and the cyst
stage of Pneumocystis jirovecii. Resistance has not yet been
reported.
応用例（製薬）
A semisynthetic lipopeptide derived from a fermentation
product of Aspergillus nidulans. Formulated for intravenous
infusion.
薬物動態学
C
max 100 mg 1-h infusion: c. 9 mg/L end infusion
Plasma half-life: 18–27 h
Volume of distribution: 0.6 L/kg
Plasma protein binding: 84%
Blood concentrations increase in proportion to dosage. The
steady state is achieved on the first day after a loading dose
(twice the daily maintenance dose).
Distribution
Levels in the CSF are negligible.
Metabolism and excretion
Unlike caspofungin and micafungin, anidulafungin is not metabolized by the liver, but undergoes slow non-enzymatic degradation in the blood to a peptide breakdown product which is enzymatically degraded and excreted in the feces and bile. About 30% of a dose is eliminated in the feces, of which less than 10% is unchanged drug. Less than 1% of a dose is excreted in the urine. No dosage adjustment is required in patients with hepatic or renal impairment. Anidulafungin is not cleared by hemodialysis.
臨床応用
Candidemia and certain invasive forms of candidosis
Esophageal candidosis
副作用
Occasional histamine-mediated infusion-related reactions,
injection site reactions and transient abnormalities of liver
enzymes have been reported.
アニデュラフンギン 上流と下流の製品情報
原材料
準備製品