Posaconazole

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Posaconazole
Posaconazole.svg
Posaconazole3d.png
Clinical data
Trade namesNoxafil, Posanol
AHFS/Drugs.comMonograph
MedlinePlusa607036
License data
Pregnancy
category
Routes of
administration
By mouth (oral suspension, delayed-release tablets), IV
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only
  • EU: Rx-only
Pharmacokinetic data
BioavailabilityHigh
Protein binding98 to 99%
MetabolismLiver (glucuronidation)
Elimination half-life16 to 31 hours
ExcretionFecal (71–77%) and renal (13–14%)
Identifiers
  • 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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.208.201 Edit this at Wikidata
Chemical and physical data
FormulaC37H42F2N8O4
Molar mass700.778 g·mol−1
3D model (JSmol)
  • 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 checkY
  • Key:RAGOYPUPXAKGKH-AGDNISCASA-N checkY
 ☒NcheckY (what is this?)  (verify)

Posaconazole, sold under the brand names Noxafil and Posanol is a triazole antifungal medication.[2][3]

It was approved for medical use in the United States in September 2006,[4] and is available as a generic medication.[5]

Medical uses[edit]

Posaconazole is used to treat invasive Aspergillus and Candida and fungal infections caused by Scedosporium and Fusarium species, which may occur in immunocompromised patients.[6] It is also used for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to itraconazole and/or fluconazole therapy.[6]

It is also used to treat invasive infections by Candida, Mucor, and Aspergillus species in severely immunocompromised patients.[7][8]

Clinical evidence for its utility in treatment of invasive disease caused by Fusarium species (fusariosis) is limited.[9]

It appears to be helpful in a mouse model of naegleriasis.[10]

Pharmacology[edit]

Pharmacodynamics[edit]

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.[11][12][13]

Microbiology[edit]

Posaconazole is active against the following microorganisms:[11][14]

Pharmacokinetics[edit]

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.[14][15]

References[edit]

  1. ^ a b "Posaconazole (Noxafil) Use During Pregnancy". Drugs.com. 23 April 2019. Retrieved 30 January 2020.
  2. ^ Schiller DS, Fung HB (September 2007). "Posaconazole: an extended-spectrum triazole antifungal agent". Clinical Therapeutics. 29 (9): 1862–86. doi:10.1016/j.clinthera.2007.09.015. PMID 18035188.
  3. ^ Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH (October 2008). "Posaconazole: an oral triazole with an extended spectrum of activity". The Annals of Pharmacotherapy. 42 (10): 1429–38. doi:10.1345/aph.1L005. PMID 18713852. S2CID 21777822. Retrieved 11 December 2008.[dead link]
  4. ^ "Drug Approval Package: Noxafil (Posaconazole) NDA #022003". U.S. Food and Drug Administration (FDA). Retrieved 15 August 2020.
  5. ^ "Posaconazole: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 15 August 2020.
  6. ^ a b "Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution". DailyMed. 20 March 2020. Retrieved 15 August 2020.
  7. ^ Li X, Brown N, Chau AS, López-Ribot JL, Ruesga MT, Quindos G, et al. (January 2004). "Changes in susceptibility to posaconazole in clinical isolates of Candida albicans". The Journal of Antimicrobial Chemotherapy. 53 (1): 74–80. doi:10.1093/jac/dkh027. PMID 14657086.
  8. ^ Walsh TJ, Raad I, Patterson TF, Chandrasekar P, Donowitz GR, Graybill R, et al. (January 2007). "Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: an externally controlled trial". Clinical Infectious Diseases. 44 (1): 2–12. doi:10.1086/508774. JSTOR 4485188. PMID 17143808.  – via JSTOR (subscription required)
  9. ^ Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, Kontoyiannis DP (May 2006). "Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions". Clinical Infectious Diseases. 42 (10): 1398–403. doi:10.1086/503425. PMID 16619151.
  10. ^ Colon BL, Rice CA, Guy RK, Kyle DE (March 2019). "Phenotypic Screens Reveal Posaconazole as a Rapidly Acting Amebicidal Combination Partner for Treatment of Primary Amoebic Meningoencephalitis". The Journal of Infectious Diseases. 219 (7): 1095–1103. doi:10.1093/infdis/jiy622. PMC 6420171. PMID 30358879.
  11. ^ a b 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
  12. ^ "Clinical Pharmacology Posaconazole". Retrieved 18 February 2010.
  13. ^ "Daily Med, Product Information Noxafil". Retrieved 18 February 2010.
  14. ^ a b Ashley ED, Perfect JR (October 2017). "Pharmacology of azoles". In Kauffman CA (ed.). UpToDate. Waltham, MA: UpToDate. Archived from the original on 9 February 2013. Retrieved 18 February 2010.
  15. ^ "Drugs at FDA: Noxafil" (PDF). Retrieved 18 February 2010.

External links[edit]

  • "Posaconazole". Drug Information Portal. U.S. National Library of Medicine.