Posaconazole

Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.^[7][8]

Posaconazole

Clinical data
Trade names	Noxafil, Posanol, others
AHFS/Drugs.com	Monograph
MedlinePlus	a607036
License data	EU EMA: by INN US DailyMed: Posaconazole US FDA: Posaconazole
Pregnancy category	AU: B3[1]
Routes of administration	By mouth, intravenous
ATC code	J02AC04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[2] CA: ℞-only[3] UK: POM (Prescription only)[4] US: ℞-only[5] EU: Rx-only[6]
Pharmacokinetic data
Bioavailability	Low (8 to 47% Oral)
Protein binding	98 to 99%
Metabolism	Liver (glucuronidation)
Elimination half-life	16 to 31 hours
Excretion	Fecal (71–77%) and Kidney (13–14%)
Identifiers
IUPAC name 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl)-3-furanyl]methoxy]phenyl]-1-piperazinyl]phenyl]-2-[(1S,2S)-1-ethyl-2- hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one
CAS Number	171228-49-2 Y
PubChem CID	147912
DrugBank	DB01263 Y
ChemSpider	130409 Y
UNII	6TK1G07BHZ
KEGG	D02555 Y
ChEBI	CHEBI:64355 N
ChEMBL	ChEMBL1397 N
CompTox Dashboard (EPA)	DTXSID6049066
ECHA InfoCard	100.208.201
Chemical and physical data
Formula	C37H42F2N8O4
Molar mass	700.792 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(/N=C\N1c2ccc(cc2)N7CCN(c6ccc(OCC3C[C@@](OC3)(c4ccc(F)cc4F)Cn5ncnc5)cc6)CC7)[C@@H](CC)[C@@H](O)C
InChI InChI=1S/C37H42F2N8O4/c1-3-35(26(2)48)47-36(49)46(25-42-47)31-7-5-29(6-8-31)43-14-16-44(17-15-43)30-9-11-32(12-10-30)50-20-27-19-37(51-21-27,22-45-24-40-23-41-45)33-13-4-28(38)18-34(33)39/h4-13,18,23-27,35,48H,3,14-17,19-22H2,1-2H3/t26-,27?,35-,37-/m0/s1 Y Key:RAGOYPUPXAKGKH-AGDNISCASA-N Y
NY (what is this?)  (verify)

It was approved for medical use in the European Union in October 2005,^[6] and in the United States in September 2006.^[5][9] It is available as a generic medication.^[10][11]

Medical uses

Posaconazole is used to treat invasive Aspergillus and Candida infections.^[5] It is also used for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to other drugs such as itraconazole and fluconazole.^[5]

Clinical evidence of efficacy in treatment of invasive disease caused by Fusarium species (fusariosis) is limited.^[12]

It appears to be helpful in a mouse model of naegleriasis^[13] and kills Acanthamoeba castellanii cysts in vitro.^[14]

It has been used to treat mucormycosis (black fungus disease) caused by Rhizopus mold. ^[15]

Pharmacology

Pharmacodynamics

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, thus inhibiting growth of the fungi. It does this by blocking the synthesis of ergosterol 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.^[5][16][17]

Microbiology

Posaconazole is active against the following microorganisms:^[16][18]

• Candida spp.
• Aspergillus spp.
• Zygomycetes spp. ^{[clarification needed]}

Pharmacokinetics

Posaconazole is absorbed within three to five hours. It is predominantly eliminated through the liver, and has a half-life of about 35 hours. Oral administration of posaconazole taken with a high-fat meal exceeds 90% bioavailability and increases the concentration by four times compared to fasting state.^[5][18]