Posaconazole, sold under the brand name Noxafil among others, is a

triazole A triazole is a heterocyclic compound featuring a five-membered ring of two carbon atoms and three nitrogen atoms with molecular formula C2H3N3. Triazoles exhibit substantial isomerism, depending on the positioning of the nitrogen atoms within ...

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 cryp ...

. It was approved for medical use in the United States in September 2006, and is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

Medical uses

Posaconazole is used to treat 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, Mic ...

'' and '' Candida'' infections. It is also used for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to

itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mo ...

and/or

fluconazole Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidiodomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and pityriasis versicolor. It is also used to prev ...

therapy. It is also used to treat invasive infections by ''Candida'', ''

Mucor ''Mucor'' is a microbial genus of approximately 40 species of molds in the family Mucoraceae. Species are commonly found in soil, digestive systems, plant surfaces, some cheeses like Tomme de Savoie, rotten vegetable matter and iron oxide re ...

'', and ''Aspergillus'' species in severely immunocompromised patients. Clinical evidence for its utility in treatment of invasive disease caused by ''

Fusarium ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil mi ...

'' species (

fusariosis Fusariosis is an infection seen in people with low neutrophils, a type of white blood cell that fights infection. It is a significant opportunistic pathogen in people with blood cancer. It is associated with infections with ''Fusarium ''Fusari ...

) is limited. It appears to be helpful in a

mouse model A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the working ...

naegleriasis Naegleriasis (also known as primary amoebic meningoencephalitis; PAM) is an almost invariably fatal infection of the brain by the free-living unicellular eukaryote ''Naegleria fowleri''. Symptoms are meningitis-like and include headache, fever ...

Pharmacology

Pharmacodynamics

Posaconazole works by disrupting the close packing of acyl chains of

phospholipids Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids ...

, impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus inhibiting growth of the fungi. It does this by blocking the synthesis of

ergosterol Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in cell membranes of fungi and protozoa, serving many of the same functions that cholesterol serves in animal cells. Because many fungi and protozoa cannot survive without ergosterol, t ...

by inhibiting of the enzyme

lanosterol 14α-demethylase Lanosterol 14α-demethylase (CYP51A1) is the animal version of a cytochrome P450 enzyme that is involved in the conversion of lanosterol to 4,4-dimethylcholesta-8(9),14,24-trien-3β-ol. The cytochrome P450 isoenzymes are a conserved group of ...

and accumulation of methylated sterol precursors. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than

.Brunton L, Lazo J, Parker K. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. San Francisco: McGraw-Hill; 2006.

Microbiology

Posaconazole is active against the following microorganisms: * '' Candida'' spp. * ''

'' spp. * '' Zygomycetes'' spp.

Pharmacokinetics

Posaconazole is absorbed within three to five hours. It is predominantly eliminated through the liver, and has a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

of about 35 hours. Oral administration of posaconazole taken with a high-fat meal exceeds 90%

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

and increases the concentration by four times compared to fasting state.

References

External links

* * {{Portal bar , Medicine 1,2,4-Triazol-3-ones 27-Hydroxylase inhibitors CYP3A4 inhibitors Fluoroarenes Lanosterol 14α-demethylase inhibitors Merck & Co. brands Orphan drugs Para-Methoxyphenylpiperazines Phenylethanolamine ethers Schering-Plough brands Secondary alcohols Tetrahydrofurans Triazole antifungals Ureas