Posaconazole

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Posaconazole
Posaconazole.svg
Posaconazole3d.png
Clinical data
Trade names Noxafil, Posanol, others
AHFS/Drugs.com Monograph
MedlinePlus a607036
License data
Pregnancy
category
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
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
  • 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 InfoCard 100.208.201 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C37H42F2N8O4
Molar mass 700.792 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 Yes check.svgY
  • Key:RAGOYPUPXAKGKH-AGDNISCASA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Contents

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]

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]

References

  1. ↑ "Posaconazole (Noxafil) Use During Pregnancy". Drugs.com. 23 April 2019. Archived from the original on 30 January 2020. Retrieved 30 January 2020.
  2. ↑ "Posaconazole suspension ARX/Posaconazole TIH/APX-Posaconazole (Arrow Pharma Pty Ltd)". Therapeutic Goods Administration (TGA). 16 February 2023. Archived from the original on 18 March 2023. Retrieved 29 April 2023.
  3. ↑ "Posanol Product information". Health Canada. 25 April 2012. Archived from the original on 16 May 2021. Retrieved 3 July 2022.
  4. ↑ "Noxafil 100 mg Gastro-resistant Tablets - Summary of Product Characteristics (SmPC)". (emc). 10 January 2022. Archived from the original on 24 February 2022. Retrieved 3 July 2022.
  5. 1 2 3 4 5 6 "Noxafil- posaconazole suspension Noxafil- posaconazole tablet, coated Noxafil- posaconazole solution". DailyMed. 20 March 2020. Archived from the original on 26 February 2021. Retrieved 15 August 2020.
  6. 1 2 "Noxafil EPAR". European Medicines Agency. 28 March 2007. Archived from the original on 19 October 2021. Retrieved 3 July 2022.
  7. ↑ 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.
  8. ↑ 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 ]
  9. ↑ "Drug Approval Package: Noxafil (Posaconazole) NDA #022003". U.S. Food and Drug Administration (FDA). 9 November 2006. Archived from the original on 3 April 2021. Retrieved 15 August 2020.
  10. ↑ "Posaconazole: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 20 October 2020. Retrieved 15 August 2020.
  11. ↑ "First Generic Drug Approvals". U.S. Food and Drug Administration. 17 October 2022. Archived from the original on 26 January 2021. Retrieved 28 November 2022.
  12. ↑ Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, et al. (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.
  13. ↑ 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.
  14. ↑ Iovieno A, Miller D, Ledee DR, Alfonso EC (September 2014). "Cysticidal activity of antifungals against different genotypes of Acanthamoeba". Antimicrob Agents Chemother. 58 (9): 5626–8. doi:10.1128/AAC.02635-14. PMC   4135811 . PMID   25001304.
  15. ↑ Fatemizadeh R, Rodman E, Demmler-Harrison GJ, Dinu D (April 2020). "Rhizopus Infection in a Preterm Infant: A Novel Use of Posaconazole". Pediatr Infect Dis J. 39 (4): 310–312. doi:10.1097/INF.0000000000002554. PMID   32084112.
  16. 1 2 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
  17. ↑ "Clinical Pharmacology Posaconazole". Archived from the original on 30 August 2021. Retrieved 18 February 2010.
  18. 1 2 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.
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