This class has only example, flucytosine. This small molecule is a DNA substrate analog that leads to incorrect DNA synthesis. Flucytosine

Fungal Cell Structure and Targets Knowledge of fungal cell structure and function is essential for understanding the pharmacology of antifungal agents. Like mammalian cells, fungi are eukaryotes with DNA organized into chromosomes within the cell nucleus and have distinct cytoplasmic organelles including endoplasmic reticulum, Golgi apparatus, mitochondria, and storage vacuoles. This homology to mammalian cells also extends to biosynthetic pathways, where fungi share similar mechanisms for DNA replication and protein synthesis. The similarity of fungal and mammalian cells creates a number of problems for designing drugs that are selectively toxic to fungal cells but not the human host. Antifungal agents […]

Background Drug interactions can arise with virtually any antifungal therapy and occur primarily in the gastrointestinal tract, liver and kidneys by several distinct mechanisms. The majority of drug interactions are pharmacokinetic in nature, resulting in changes in the absorption or elimination of the interacting drug as well as the antifungal agent [922]. In the GI tract, changes in pH, complexation with ions, or interference with transport and enzymatic processes in the intestinal lumen can interfere with drug absorbance. Induction or inhibition of metabolism in the liver can inhibit or accelerate, respectively, drug clearance from the body. In the kidney, decreases […]

Antifungal Dosage Adjustment in Hepatic Failure A number of antifungals require biotransformation into more water-soluble metabolites by the liver before excretion from the body. Antifungals are also known to have, like many other drugs, potentially toxic effects in the liver that may be enhanced with pre-existing liver disease. Therefore, antifungal therapy must be used in caution in patients with hepatic insufficiency. In terms of drug dosing, patients with moderate to severe hepatic dysfunction often exhibit a decreased capacity to metabolize certain antifungal agents, leading to decreased overall drug clearance, an increase in the plasma/serum area under the concentration curve (AUC), […]

Background Like many other medications, dosages of antifungal agents may be adjusted in patients with compromised kidney or liver function to minimize potential toxicities associated with drug accumulation. Drug interactions can also require a change in antifungal dosing. Fortunately, the effects of impaired kidney and liver function on antifungal concentrations in the body can be anticipated based on the pharmacokinetic properties of the specific antifungal agent; i.e. its absorption, distribution, and pathway for elimination from the body. In certain situations, measuring the serum drug concentration of an antifungal agent can provide some guidance for dosage adjustment or in the assessment […]

A number of different antifungal agents are available. Agents in use for humans and animals are sometimes used in environmental, industrial and agricultural settings, but there are agents that are useful on plants but not humans or animals. Generally speaking, the available agents can be classified as follows: Allylamines and other non-azole ergosterol biosynthesis inhibitors: These agents act in a variety of fashions, but fundamentally all lead to reduced ergosterol biosynthesis and are thus conceptually related to the azole antifungal agents. One example is terbinafine, which acts by inhibiting squalene epoxidase. Antimetabolites: This class has only one example, flucytosine. This […]

Anidulafungin (Praxis®) Manufacturer’s Prescribing Information Trade & Generic Names & General Features Anidulafungin (previously known as LY303366 and briefly also referred to as VER-002 and V-echinocandin) is a glucan synthase inhibitor of the echinocandin structural class. It is composed of the echinocandin B nucleus with a terphenyl head group and a C5 tail. Anidulafungin was initially developed by Eli Lilly Pharmaceuticals. It was subsequently licensed to Versicor for development as a parenteral agent and the name of the manufacturing company thereafter changed to Vicuron.  Pfizer acquired the drug upon its acquisition of Vicuron in the fall of 2005.  It received FDA approval in February […]

Trade & Generic Names & General Features Amphotericin B lipid complex (ABLC) is a lipid formulation of amphotericin B. As with the other lipid formulations, the major goal of developing ABLC has been to attain a compound with lower toxicity and with at least similar efficacy compared to the parent compound, amphotericin B deoxycholate. ABLC is composed of amphotericin B complexed with dymyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol [1044, 2454]. The configuration of this complex is ribbon-like. ABLC is now being manufactured by Enzon Pharmaceuticals (Fairfield, New Jersey, USA) and its trade name is Abelcet. Amphotericin B concentrations achieved in blood […]

Manufacturer’s Prescribing Information Trade & Generic Names & General Features Amphotericin B is a polyene antifungal agent, first isolated by Gold et al from Streptomyces nodosus in 1955. It is an amphoteric compound composed of a hydrophilic polyhydroxyl chain along one side and a lipophilic polyene hydrocarbon chain on the other. Amphotericin B is poorly soluble in water [2232]. Amphotericin B is now available in four formulations. The classic amphotericin B deoxycholate (Fungizone™) formulation has been available since 1960 and is a colloidal suspension of amphotericin B. A bile salt, deoxycholate, is used as the solubilizing agent. This preparation has […]

Trade & Generic Names & General Features Amphotericin B colloidal dispersion (ABCD) is a lipid formulation of amphotericin B. As with the other lipid formulations, the major goal of developing ABCD has been to attain a compound with lower toxicity and with at least similar efficacy compared to the parent compound, amphotericin B deoxycholate. ABCD is composed of amphotericin B complexed with cholesteryl sulfate. It is a disk-like structure [939, 1044]. ABCD is being manufactured by Sequus Pharmaceuticals (Menlo Park, CA, USA) under two trade names, Amphocil™ and Amphotec™. ABCD displays two-compartment pharmacokinetics. After infusion, it is rapidly removed from […]

Oral amphotericin B Trade & Generic Names & General Features Oral capsule and suspension forms of amphotericin B can be compounded or are available commercially. These formulations are poorly absorbed. Mechanism(s) of Action The antifungal activity of oral amphotericin B is via the mechanism noted for other amphotericin B formulations. It binds to sterols, preferentially to the primary fungal cell membrane sterol, ergosterol. This binding disrupts osmotic integrity of the fungal membrane, resulting in leakage of intracellular potassium, magnesium, sugars, and metabolites and then cellular death [2232]. Usual Doses There is yet no validated standard dose of oral amphotericin B. […]

Trade & Generic Names & General Features Amorolfine is a morpholine derivative which is used topically as an antifungal agent. It has a broad spectrum of activity, including dermatophytes, various filamentous and dematiaceous fungi, yeasts and dimorphic fungi. Its activity is fungicidal for most species [451, 984, 1818]. It penetrates into the nail rapidly and achieves concentrations higher than the MICs obtained for most of the fungi causing onychomycosis. [1002, 1817, 2246]. Its clearance is slow following topical application [1962]. Amorolfine has been ineffective when administered orally to animals with systemic fungal infections. This lack of activity may be due […]

Allylamines are organic compounds with the formula C3H5NH2 These agents act by inhibiting squalene epoxidase. This is another enzyme in the pathway that leads to synthesis of ergosterol, so this agent is conceptually related to the azole antifungal agents. Terbinafine Naftifine