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 accommo ...
)
(trade names Eraxis, Ecalta) is a
semisynthetic
Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
echinocandin used as an
antifungal drug
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 crypto ...
. It was previously known as LY303366. 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, Mich ...
'' infection when used in combination with
voriconazole
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ' ...
. It is a member of the class of antifungal drugs known as the
echinocandins; 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.
Indications
*
Candidemia
Fungemia is the presence of fungi or yeasts 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 of ...
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. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...
and
peritonitis)
*
Esophageal candidiasis
Anidulafungin has not been studied in
endocarditis,
osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
, 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, headache, and neck stiffness. Other symptoms include confusion or ...
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 bacteri ...
patients to determine efficacy in this group.
Pharmacodynamics and pharmacokinetics
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.
Volume of distribution
In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...
: 30–50 L.
Anidulafungin is not evidently metabolized by the
liver. This specific drug undergoes slow chemical
hydrolysis 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 produced these molecules as a part of their metabolism, especially those of the genus '' Bacillus'', ...
fermentation product of ''
Aspergillus nidulans
''Aspergillus nidulans'' (also called ''Emericella nidulans'' when referring to its sexual form, or teleomorph) is one of many species of filamentous fungi in the phylum Ascomycota. It has been an important research organism for studying eukaryot ...
'' 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 acquired the drug upon its acquisition of Vicuron in the fall of 2005. Pfizer gained approval by the
Food and Drug Administration (FDA) on February 21, 2006.
References
{{Antifungals
Antifungals
Echinocandins
Pfizer brands
World Health Organization essential medicines