Анидулафунгин

Описание

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 While the first member of this class, cilofungin, was withdrawn due to toxicity associated with the formulation vehicle, anidulafungin follows the successful introduction of caspofungin and micafungin.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.

Использование

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.

Определение

ChEBI: A semisynthetic echinocandin anti-fungal drug. It is active against Aspergillus and Candida species and is used for the treatment of invasive candidiasis.

Антимикробная активность

It is active against Aspergillus spp., Candida spp. and the cyst stage of Pneumocystis jirovecii. Resistance has not yet been reported.

Фармацевтические приложения

A semisynthetic lipopeptide derived from a fermentation product of Aspergillus nidulans. Formulated for intravenous infusion.

Фармакокине?тика

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.

Клиническое использование

Candidemia and certain invasive forms of candidosis
Esophageal candidosis

Побочные эффекты

Occasional histamine-mediated infusion-related reactions, injection site reactions and transient abnormalities of liver enzymes have been reported.