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 United States in September 2006, [5] [9] and 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 itraconazole and/or fluconazole therapy. [5]

It is also used to treat invasive infections by Candida, Mucor , and Aspergillus species in severely immunocompromised patients. [12] [13]

Clinical evidence for its utility in treatment of invasive disease caused by Fusarium species (fusariosis) is limited. [14]

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

Related Research Articles

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An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.

<span class="mw-page-title-main">Itraconazole</span> Chemical compound used as medication to treat fungal infections

Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth or intravenously.

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<span class="mw-page-title-main">Ketoconazole</span> Antifungal chemical compound

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<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

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<span class="mw-page-title-main">Caspofungin</span> Antifungal medication

Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall. Caspofungin was the first inhibitor of fungal (1→3)-β-D-glucan synthesis to be approved by the United States Food and Drug Administration. Caspofungin is administered intravenously.

<span class="mw-page-title-main">Terconazole</span> Chemical compound

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<span class="mw-page-title-main">Aspergillosis</span> Medical condition

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References

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  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.
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  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.
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  13. 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)
  14. 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.
  15. 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.
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