Posaconazole

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Posaconazole
Posaconazole.svg
Posaconazole3d.png
Systematic (IUPAC) name
4-(4-(4-(4-(((3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-2-((2S,3S)-2-hydroxypentan-3-yl)-1,2,4-triazol-3-one
Clinical data
Trade names Noxafil, Posanol
AHFS/Drugs.com monograph
MedlinePlus a607036
Licence data EMA:Link, US FDA:link
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Legal status
Routes of
administration		 Oral
Pharmacokinetic data
Bioavailability High
Protein binding 98 to 99%
Metabolism Hepatic glucuronidation
Biological half-life 16 to 31 hours
Excretion Fecal (77%) and renal (14%)
Identifiers
CAS Number 171228-49-2 YesY
ATC code J02AC04 (WHO)
PubChem CID: 147912
DrugBank DB01263 YesY
ChemSpider 130409 YesY
UNII 6TK1G07BHZ YesY
KEGG D02555 YesY
ChEBI CHEBI:64355 N
ChEMBL CHEMBL1397 N
Synonyms 4-{4-[4-(4-{[(5R)-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-1-[(2S,3S)-2-hydroxypentan-3-yl]-4,5-dihydro-1H-1,2,4-triazol-5-one
Chemical data
Formula C37H42F2N8O4
Molecular mass 700.778 g/mol
  • 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=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 YesY
  • Key:RAGOYPUPXAKGKH-AGDNISCASA-N YesY
 NYesY (what is this?)  (verify)

Posaconazole is a triazole antifungal drug.[1][2] It 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.

Medical uses

It is used to treat invasive infections by Candida species, Mucor, and Aspergillus species in severely immunocompromised patients.[3][4]

Clinical evidence for its utility in treatment of invasive disease caused by Fusarium species (fusariosis) is limited.[5]

Pharmacology

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, 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.[6][7][8]

Microbiology

Posaconazole is active against the following microorganisms:[6][9]

Pharmacokinetics

Posaconazole is absorbed within three to five hours. It is predominately 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.[9][10]

Research

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.[11] Schering-Plough is currently recruiting participants for a phase 2 clinical trial in Argentina to test its efficacy against asymptomatic, chronic Chagas.[12]

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.  – via JSTOR (subscription required)
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 Brunton L, Lazo J, Parker K. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. San Francisco: McGraw-Hill; 2006. ISBN 978-0-07-142280-2
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ "Am J Trop Med Hyg April 2010 vol. 82 no. 4"
  12. ↑ "A Study of the Use of Oral Posaconazole (POS) in the Treatment of Asymptomatic Chronic Chagas Disease (P05267 AM1) (STOP CHAGAS)"
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