Anidulafungin (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

) (sold under the brand name Eraxis among others, is a semisynthetic

echinocandin Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been dubbed the "penicillin of antifungals," along w ...

used as an

antifungal medication An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cry ...

. It may also have application in treating invasive ''

Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Miche ...

'' infection when used in combination with voriconazole. It is a member of the class of antifungal drugs known as the

s; its mechanism of action is by inhibition of (1→3)-β-D-glucan synthase, an enzyme important to the synthesis of the fungal cell wall. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Indications

Candidemia Fungemia is the presence of fungi or yeast in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by '' Candida'' species. Candidemia is also among the most common bloodstream infections ...

and other forms of invasive ''Candida'' infections (intra-abdominal

abscess An abscess is a collection of pus that has built up within the tissue of the body, usually caused by bacterial infection. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pre ...

and

peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and covering of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One pa ...

) * Esophageal candidiasis Anidulafungin has not been studied in

endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, o ...

osteomyelitis Osteomyelitis (OM) is the infectious inflammation of bone marrow. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The feet, spine, and hips are the most commonly involved bones in adults. The cause is ...

, and

meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...

due to ''Candida'', and has not been studied in sufficient numbers of

neutropenic Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

patients to determine efficacy in this group.

Pharmacology

Pharmacodynamics

Anidulafungin significantly differs from other antifungals in that it undergoes chemical degradation to inactive forms at body pH and temperature. Because it does not rely on enzymatic degradation or hepatic or renal excretion, the drug is safe to use in patients with any degree of hepatic or renal impairment.

Pharmacokinetics

Anidulafungin is not evidently metabolized by the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. This specific drug undergoes slow chemical

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

to an open-ring peptide which lacks antifungal activity. The half-life of the drug is 27 hours. About 30% is excreted in the feces (10% as unchanged drug). Less than 1% is excreted in the urine.

Mechanism of action

Anidulafungin inhibits glucan synthase, an enzyme important in the formation of (1→3)-β-D-glucan, a major fungal cell wall component. Glucan synthase is not present in mammalian cells, so it is an attractive target for antifungal activity.

Semisynthesis

Anidulafungin is manufactured via semi-synthesis. The starting material is echinocandin B (a

lipopeptide A lipopeptide is a molecule consisting of a lipid connected to a peptide. They are able to self-assemble into different structures. Many bacteria produce these molecules as a part of their metabolism, especially those of the genus ''Bacillus'', ...

fermentation product of '' Aspergillus nidulans'' or the closely related species, ''A. rugulosus''), which undergoes deacylation (cleavage of the linoleoyl side chain) by the action of a deacylase enzyme from the bacterium '' Actinoplanes utahensis''; in three subsequent synthetic steps, including a chemical reacylation, the antifungal drug anidulafungin is synthesized.

History

Anidulafungin was originally discovered at Lilly laboratories by Turner and Debono and licensed to Vicuron Pharmaceuticals who submitted it to the FDA.

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

acquired the drug upon its acquisition of Vicuron in the fall of 2005. Pfizer gained approval by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) on 21 February 2006.

References

{{Antifungals Antifungals Echinocandins Drugs developed by Pfizer World Health Organization essential medicines Pentyl compounds