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Posaconazole

Posaconazole
Posaconazole.svg
Posaconazole3d.png
Clinical data
Trade namesNoxafil, Posanol
Synonyms4-{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
AHFS/Drugs.comMonograph
MedlinePlusa607036
License data
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration
By mouth (oral suspension, delayed-release tablets), IV
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityHigh
Protein binding98 to 99%
MetabolismLiver (glucuronidation)
Elimination half-life16 to 31 hours
ExcretionFecal (71–77%) and renal (13–14%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.208.201 Edit this at Wikidata
Chemical and physical data
FormulaC37H42F2N8O4
Molar mass700.778 g/mol g·mol−1
3D model (JSmol)
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Posaconazole (trade name Noxafil, Posanol) is a triazole antifungal drug.[1][2]

Medical uses

Posaconazole is used to treat invasive aspergillosis and candidiasis and fungal infections caused by Scedosporium and Fusarium species, which may occur in immunocompromised patients. It is also used for the treatment of oropharyngeal candidiasis (OPC), including OPC refractory to itraconazole and/or fluconazole therapy.[3]

It is also used to treat invasive infections by Candida, Mucor, and Aspergillus species in severely immunocompromised patients.[4][5]

Clinical evidence for its utility in treatment of invasive disease caused by Fusarium species (fusariosis) is limited.[6]

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.[7][8][9]

Microbiology

Posaconazole is active against the following microorganisms:[7][10]

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.[10][11]

See also

References

  1. ^ Schiller DS, Fung HB (September 2007). "Posaconazole: an extended-spectrum triazole antifungal agent". Clin Ther. 29 (9): 1862–86. doi:10.1016/j.clinthera.2007.09.015. PMID 18035188.
  2. ^ Rachwalski EJ, Wieczorkiewicz JT, Scheetz MH (October 2008). "Posaconazole: an oral triazole with an extended spectrum of activity". Ann Pharmacother. 42 (10): 1429–38. doi:10.1345/aph.1L005. PMID 18713852.
  3. ^ "Noxafil (posaconazole) Injection 18 mg/mL, Delayed-Release Tablets 100 mg and Oral Suspension 40 mg/mL. Full Prescribing Information" (PDF). Merck & Co., Inc., Whitehouse Station, NJ 08889, USA. Retrieved 27 August 2016.
  4. ^ Li X, Brown N, Chau AS, et al. (January 2004). "Changes in susceptibility to posaconazole in clinical isolates of Candida albicans". J. Antimicrob. Chemother. 53 (1): 74–80. doi:10.1093/jac/dkh027. PMID 14657086.
  5. ^ Walsh TJ, Raad I, Patterson TF, 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". Clin. Infect. Dis. 44 (1): 2–12. doi:10.1086/508774. JSTOR 4485188. PMID 17143808.  – via JSTOR (subscription required)
  6. ^ Raad I, Hachem R, Herbrecht R, et al. (2006). "Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions". Clin Infect Dis. 42 (10): 1398–1403. doi:10.1086/503425. PMID 16619151.
  7. ^ 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
  8. ^ "Clinical Pharmacology Posaconazole". Retrieved 18 February 2010.
  9. ^ "Daily Med, Product Information Noxafil". Retrieved 18 February 2010.
  10. ^ a b Dodds Ashley, Elizabeth; Perfect, John (October 13, 2009). "Pharmacology of azoles". Retrieved 18 February 2010.
  11. ^ "Drugs at FDA: Noxafil" (PDF). Retrieved 18 February 2010.