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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Systemically administered antifungal agents. A review of their clinical pharmacology and therapeutic applications.

Systemic antifungal agents express great diversity in their pharmacokinetic profiles, mechanisms of action, and toxicities. Understanding the diverse pharmacokinetic properties of systemic antifungals is critical to their appropriate application. Amphotericin B, drug of choice for most invasive mycoses, has unique pharmacokinetic properties, binding initially to serum lipoproteins and redistributing from blood to tissues. Dosing recommendations are based on the specific infection and the status of the host. Lipid formulations of amphotericin B may be able to attenuate some of its toxicities. Flucytosine is a water-soluble, fluorinated pyrimidine that possesses excellent bioavailability. It is administered only in combination with amphotericin B because of frequent development of secondary drug resistance, and is associated with dose-dependent bone marrow suppression. The antifungal azoles are relatively well tolerated, have broad spectrum antifungal activity, and are fungistatic in vitro. Ketoconazole and itraconazole are highly bound to plasma proteins, are extensively metabolised by the liver, and are relatively insoluble in aqueous solution. By comparison, fluconazole is only weakly bound to serum proteins, is relatively stable to metabolic conversion, and is water soluble. Fluconazole penetrates the cerebrospinal fluid well and is approved for primary and suppressive therapy of cryptococcal meningitis in AIDS patients. The echinocandins have a narrow spectrum of antifungal activity, being effective only against Candida spp.[1]

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