Anidulafungin is an echinocandin anti-fungal agent used for intravenous (IV) infusion. It is chemically designated as C58H73N7O17, and its molecular weight is 1140.3. This white to off-white lyophilized powder is available as a single-use, 50-mg vial that is supplied with an accompanying 15-ml diluent vial (20% weight in weight [w/w] dehydrated alcohol in water, or 20 g/100 g).
Figure 1 illustrates the agent’s chemical structure.
Figure 1 Chemical structure of anidulafungin. (From Eraxis product information.)
As a semisynthetic lipopeptide, ani-dulafungin is synthesized from a fermentation product of Aspergillus nidulans. It possesses potent fungicidal activity against most Candida species, including those resistant to azoles. Anidulafungin also has in vitro activity against Asper-gillus, but it is less active against other filamentous fungi.
MECHANISM OF ACTION
The activity of anidulafungin is similar to that of other antifungal agents; it interferes with the synthesis of the fungal cell wall. As with all agents of the echino-candin class, its spectrum of activity is largely limited to Candidaand Aspergillus species.
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Anidulafungin exerts its antifungal activity by noncompetitively inhibiting 1,3-p-D-glucan synthase, which results in inhibition of glucan synthesis. Glucan is an essential component of the fungal cell wall, making it a selective target for anti-fungal agents.
The pharmacokinetic parameters in 225 patients with fungal infections were similar to those found in healthy subjects (Table 1).
Table 1 Mean (Percent Coefficient of Variation) Steady-State Pharmacokinetic Parameters
|Parameter||Loading Dose, Loading Dose, 100 mg 200 mgMaintenance Dose, Maintenance Dose, 50 mg 50 mg|
|C (mg/liter)max о >||4.2 (22.4)||7.2 (23.3)|
|C (mg/liter)||1.6 (42.1)||3.3 (41.8)|
|AUCss (mg • hours/liter)||55.2 (32.5)||110.3 (32.5)|
|Clearance (liters/hour)||1.0 (33.5)|
|Half-life (hours)||26.5 (28.5)|
|AUCss = steady-state area under the curve; Cmax = steady-state peak concentration; Cmin = steady-state minimum concentration. From Eraxis product information.8|
Steady state is achieved on the first day of treatment following a loading dose of anidulafungin. The volume of distribution is similar to total body fluid volume at 30 to 50 liters. Binding to plasma protein is moderate at 84%. cialis canadian pharmacy
Anidulafungin does not appear to go through hepatic metabolism. It is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP 450) isoenzymes.
Table 2 presents the results of some drug-interaction studies.
Table 2 Drug Interactions and Anidulafungin
|Cyclosporine||3A4 substrate||Cmax of anidulafungin not significantly alteredAUC increased by 22%
No effect on cyclosporine metabolism
|Voriconazole(Vfend)||3A4 inhibitor and substrate Neither Cmax nor AUC of either drug significantly altered 2C19,2C9||
|Tacrolimus generic (Canadian Prograf capsules or injection)||3A4 substrate||Neither Cmax nor AUC of either drug significantly altered||
|Liposomal ampho-tericin B (AmBisome)||—||Pharmacokinetics of anidulafungin not significantly altered||
|Rifampin||Potent CYP inducer||Pharmacokinetics of anidulafungin not significantly altered||
|AUC = area-under-the-curve concentration; Cmax =’ max
From Eraxis product information.
|peak concentration; CYP = cytochrome.|
More than 90% of anidulafungin undergoes a slow chemical degradation in the blood, and the agent’s half-life is approximately 24 hours. No dose adjustments are needed in patients with renal or hepatic impairment because most degradation products are eliminated via the biliary system.