Posaconazole
Encyclopedia
Posaconazole is a triazole
antifungal drug.
Posaconazole is marketed in the United States, the European Union, and in other countries by Schering-Plough
under the trade name Noxafil. In Canada, posaconazole is marketed by Schering-Plough under the trade name Posanol.
by inhibiting of the enzyme lanosterol
14α-demethylase and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole
.
and increases the concentration by 4 times compared to fasting state.
species, Mucor, and Aspergillus
species in severely immunocompromised
patients.
There is also limited clinical evidence for its utility in treatment of invasive disease caused by Fusarium
species (fusariosis
).
Two studies published in the January 25, 2007 issue of the New England Journal of Medicine
suggest posaconazole may be superior to other triazoles, such as fluconazole
or itraconazole
, in the prevention of invasive fungal infections, although it may cause more serious side effects
.
There is also some indication that posaconazole may be the most effective treatment for both chronic and acute Chagas disease, showing much better efficacy than Benznidazole. Schering-Plough is currently recruiting participants for a phase 2 clinical trial in Argentina to test its efficacy against against asymptomatic, chronic Chagas.
Triazole
Triazole refers to either one of a pair of isomeric chemical compounds with molecular formula C2H3N3, having a five-membered ring of two carbon atoms and three nitrogen atoms.The two isomers are:*1,2,3-Triazole 100px*1,2,4-Triazole 100px...
antifungal drug.
Posaconazole is marketed in the United States, the European Union, and in other countries by Schering-Plough
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
under the trade name Noxafil. In Canada, posaconazole is marketed by Schering-Plough under the trade name Posanol.
Mode of action
Posaconazole works by disrupting the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system and thus inhibiting growth of the fungi. It does this by blocking the synthesis of ergosterolErgosterol
Ergosterol is a sterol found in fungi, and named for ergot, a common name for the members of the fungal genus Claviceps from which ergosterol was first isolated. Ergosterol does not occur in plant or animal cells...
by inhibiting of the enzyme lanosterol
Lanosterol
Lanosterol is a tetracyclic triterpenoid, which is the compound from which all steroids are derived.-Role in creation of steroids:Elaboration of lanosterol under enzyme catalysis leads to the core structure of steroids. 14-Demethylation of lanosterol by CYP51 eventually yields...
14α-demethylase and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
.
Microbiology
Posaconazole is active against the following microorganisms:- CandidaCandida (genus)Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...
spp. - AspergillusAspergillusAspergillus 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...
spp. - Zygomycetes spp.
Pharmacokinetics
Posaconazole is absorbed within 3-5 hours. Posaconazole is predominately eliminated through the liver and has a half life of about 35 hours. Oral administration of Posconazole taken with a high fat meal exceeds 90% bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
and increases the concentration by 4 times compared to fasting state.
Clinical use
It is used to treat invasive infections by CandidaCandida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...
species, Mucor, and Aspergillus
Aspergillus
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...
species in severely immunocompromised
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
patients.
There is also limited clinical evidence for its utility in treatment of invasive disease caused by Fusarium
Fusarium
Fusarium is a large genus of filamentous fungi widely distributed in soil and in association with plants. Most species are harmless saprobes, and are relatively abundant members of the soil microbial community. Some species produce mycotoxins in cereal crops that can affect human and animal health...
species (fusariosis
Fusariosis
Fusariosis is an infection seen in neutropenic patients, and is a significant opportunistic pathogen in patients with hematologic malignancy.It is associated with infections with Fusarium species, such as Fusarium proliferatum....
).
Two studies published in the January 25, 2007 issue of the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
suggest posaconazole may be superior to other triazoles, such as fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
or itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
, in the prevention of invasive fungal infections, although it may cause more serious side effects
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
.
There is also some indication that posaconazole may be the most effective treatment for both chronic and acute Chagas disease, showing much better efficacy than Benznidazole. Schering-Plough is currently recruiting participants for a phase 2 clinical trial in Argentina to test its efficacy against against asymptomatic, chronic Chagas.