ミカファンギン 化學特性,用途語,生産方法
用途
キャンデイン系抗真菌薬真菌特有の細胞壁構(gòu)成成分β-1,3-グルカンの合成酵素を阻害する
効能
抗真菌薬, 細胞壁合成阻害薬
説明
Micafungin, the second
member of the echinocandin
class of antifungal agents was
launched in Japan for
the parenteral treatment of
various fungal infections caused
by Aspergillus and Candida spp.
such as fungaemia and
respiratory and gastrointestinal
mycoses. This water-soluble
semisynthetic cyclic lipopeptide is synthesized by acylation with (5-(4-
pentyloxyphenyl)isoxazol-3-yl)benzoate of the cyclic peptide nucleus (FR-179642).obtained by enzymatic cleavage of the naturally occurring echinocandin FR-901379,
derived from the fungus Coleophoma empedri Micafungin acts by inhibiting the synthesis
of 1,3-beta-glucan, an essential polysaccharide of the cell wall of many pathogenic fungi.
Micafungin has a marked fungicidal effect on almost all species of Candida, including
fluconazole-resistant spp. C. albicans, C. glabrata, C. Krusei, C. parapsilosis and C.
tropicalis and a fungistatic effect on a range of Aspergillus species including A. flaws, A.
fumigates and A. terreus. Like caspofungin, micafungin is inactive against Cryptococcus
neoformans, and the emerging pathogen Trichosporon cutaneum and Fusarium solani.
Micafungin has proved highly effective in mouse models of Cancfidiasis and Aspergillus
infections (including those using an amphotericin B- and itraconazole-resistant isolate of A.
fumigatus). In phase I studies, micafungin had linear pharmacokinetics with an elimination
half-life ranging from 11.7 to 15.2 h after injection and was well tolerated.
使用
Micafungin is a semi-synthetic cyclic lipopeptide belonging to the echinocandin class that was reported in 1999 from Fujisawa in Japan. Unlike other marketed semi-synthetic derivatives in this class, micafungin is not derived from echinocandin but rather from FR901379 which contains a phenolic sulphate to enhance aqueous solubility, a serious limitation in the class. Micafungin 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 700 citations.
定義
ChEBI: A cyclic hexapeptide echinocandin antibiotic which exerts its effect by inhibiting the synthesis of 1,3-beta-D-glucan, an integral component of the fungal cell wall. It is used as the sodium salt for the treatment of invas
ve candidiasis, and of aspergillosis in patients who are intolerant of other therapy.
抗菌性
It is active against Aspergillus spp., Candida spp. and the cyst
form of Pn. jirovecii. Resistance has rarely been reported.
応用例（製薬）
A semisynthetic lipopeptide derived from a fermentation
product of Coleophoma empetri. Formulated as the monosodium
salt for intravenous infusion.
薬物動態(tài)學
C
max 50 mg 1-h infusion: c. 5 mg/L 1 h post infusion
Plasma half-life: 11–15 h
Volume of distribution: 0.4 L/kg
Plasma protein binding: 99%
Blood concentrations increase in proportion to dosage. Unlike anidulafungin and caspofungin, a loading dose is not required.
Distribution
The drug is widely distributed, the highest concentrations being found in the liver. Levels in the CSF and urine are negligible.
Metabolism and excretion
It is metabolized by the liver and the three inactive metabolites are excreted in the feces (70%). Less than 1% of a dose is eliminated as unchanged drug in the urine. No dosage adjustment is required in patients with severe renal impairment or mild to moderate hepatic impairment. The effect of severe hepatic impairment on micafungin pharmacokinetics has not been studied. Micafungin is not cleared by hemodialysis.
臨床応用
Candidemia and certain invasive forms of candidosis
Esophageal candidosis
Prophylaxis of Candida infections in hematopoietic stem cell transplant
(HSCT) recipients
副作用
Occasional histamine-mediated infusion-related reactions,
injection site reactions and transient abnormalities of liver
enzymes have been reported. Isolated cases of significant
hepatic or renal dysfunction, hepatitis, or liver or renal failure
have also been described.
ミカファンギン 上流と下流の製品情報
原材料
準備製品