Chemistry:Pentosan polysulfate

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Short description: Chemical compound
Pentosan polysulfate
Pentosan polysulfate.svg
Clinical data
Trade namesElmiron, Zycosan
Other namesPPS, (1->4)-β-Xylan 2,3-bis(hydrogen sulfate) with a 4 O-methyl-α-D-glucuronate
AHFS/Drugs.comMonograph
License data
Routes of
administration		By mouth, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
ExcretionFeces, urine[1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC10H18O21S4
Molar mass602.47 g·mol−1
3D model (JSmol)
  (verify)

Pentosan polysulfate, sold under the brand name Elmiron among others, is a medication used for the treatment of interstitial cystitis.[1] It was approved for medical use in the United States in 1996.[1][2][3]

Medical uses

Pentosan polysulfate sodium is indicated for the relief of bladder pain or discomfort associated with interstitial cystitis.[1]

Adverse effects

Patients who have taken pentosan polysulfate orally report a variety of side effects, primarily gastrointestinal complaints such as diarrhea, heartburn, and stomach pain.[4] Hair loss, headache, rash, and insomnia have also been reported.[4] Due to Elmiron's anticoagulant effects, some patients report bruising more easily. In some cases, patients are asked to stop taking the medication before any major surgical procedures to reduce the likelihood of bleeding. Recent report based on clinical observation hypothesizes that chronic exposure to pentosan polysulfate can cause retinal toxicity, mimicking pigmentary pattern dystrophy.[2][5][6][7]

Mechanism of action

In interstitial cystitis, pentosan polysulfate is believed to work by providing a protective coating to the damaged bladder wall. Pentosan polysulfate is similar in structure to the natural glycosaminoglycan coating of the inner lining of the bladder, and may replace or repair the lining, reducing its permeability.[5]

History

The calcium salt of pentosan polysulfate was one of the first reported disease-modifying osteoarthritis drugs (DMOAD).[6]

Society and culture

Names

The IUPAC name for pentosan polysulfate is [(2R,3R,4S,5R)-2-hydroxy-5-[(2S,3R,4S,5R)-5-hydroxy-3,4-disulfooxyoxan-2-yl]oxy-3-sulfooxyoxan-4-yl] hydrogen sulfate.[8]

There are 40 synonyms listed for pentosan polysulfate on PubChem including BAY-946, HOE-946, pentosan sulfuric polyester, polypentose sulfate, polysulfated xylan, PZ-68, SP-54, xylan SP54 and xylan sulfate.[9]

Various brand names include Elmiron (as sodium salt), Hemoclar, Anarthron, Fibrase, Fibrocid, Thrombocid and SP54. Pentosan polysulfate capsules are sold in India under the brand names Comfora, Pentossan-100, Cystopen and For-IC. In the veterinary field, pentosan polysulfate is sold as Cartrophen Vet and Sylvet by Biopharm Australia, Pentosan by Naturevet Australia, Anarthron by Randlab Australia and Zydax by Parnell.[10]

Research

Osteoarthritis

Pentosan polysulfate has been studied in knee osteoarthritis, though evidence to support such use is poor as of 2003.[11] There is some theoretical evidence that it should help.[12]

Transmissible spongiform encephalopathies

Pentosan polysulfate is being studied as a potential treatment of Creutzfeldt–Jakob disease (CJD). The rationale for this treatment was unclear but it was subsequently shown in prion-infected mouse neuroblastoma cells that pentosan polysulfate could rapidly reduce the levels of abnormal (scrapie) prion without affecting the normal cellular isoform.[13] As pentosan polysulfate can bind to the cellular isoform of the prion protein, it may stabilise this form and prevent its conversion to the pathological (scrapie) isoform.[14]

The treatment[15] of one patient in Northern Ireland and around six other patients in mainland Britain was reported in the press.[16]

Veterinary uses

Dogs

Read et al. (1996) [17] used three different doses of sodium pentosan polysulfate to treat 40 geriatric dogs with well-established clinical signs of chronic osteoarthritis (OA) with a subcutaneous injection. The 3 mg/kg dose was the most effective. In a study conducted with 10 elderly dogs with osteoarthritis given calcium pentosan polysulfate (3 mg/kg intramuscularly) once weekly for four weeks, the improvement in symptoms (seen at 1, 2, 3 and 7 weeks after initiation of therapy) was found to correlate with plasma indices of fibrinolytic activity and lipid profiles.[18] In a study in dogs with OA secondary to cranial cruciate ligament deficiency, although no differences were identified in either functional outcome or radiographic progression using the oral calcium pentosan polysulfate compared with placebo, there were significantly lower levels of proteoglycan breakdown products in the synovial fluid of the osteoarthritic joints.[19] The efficacy of subcutaneous sodium pentosan polysulfate (3 mg/kg) was tested in 40 dogs with cranial cruciate ligament instability and found to hasten recovery, as measured by more rapidly improved ground reaction forces, over 48 weeks.[20]

Horses

Zycosan, for horses, is a heparin-like compound and is the first injectable pentosan product to receive approval by the US Food and Drug Administration (FDA).[21]

In December 2022, the US Food and Drug Administration (FDA) approved pentosan polysulfate (Zycosan) for the control of clinical signs associated with osteoarthritis in horses.[21] Zycosan is for intramuscular use in horses only and is not for use in humans.[21] Zycosan is sponsored by Anzac Animal Health LLC, based in Maryland Heights, Missouri.[21]

Pentosan polysulfate is being used for this osteoarthritis in Australia. When administered to racing thoroughbreds with chronic osteoarthritis (2 to 3 mg/kg, intramuscularly, once weekly for 4 weeks, then as required), pentosan polysulfate treatment improved but did not eliminate clinical signs of joint disease.[22] Articular cartilage fibrillation was substantially reduced by similar NaPPS treatment intramuscularly in nine horses with experimentally-induced carpal osteoarthritis.[23]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Elmiron- pentosan polysulfate sodium capsule, gelatin coated". 10 November 2022. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0ba651e-3d8a-11df-8fbe-119855d89593. 
  2. ↑ 2.0 2.1 "Pentosan polysulfate maculopathy". Survey of Ophthalmology 67 (1): 83–96. 2022. doi:10.1016/j.survophthal.2021.05.005. PMID 34000253. 
  3. ↑ "Elmiron (pentosan polysulfate sodium)". FDA approval letter. U.S. Food and Drug Administration. 25 September 1996. https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020193Orig1s000rev.pdf. 
  4. ↑ 4.0 4.1 Pubmed Health (2012). "Pentosan Polysulfate". U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0045790/. 
  5. ↑ 5.0 5.1 "The therapeutic role of sulfated polysaccharides in the urinary bladder". The Urologic Clinics of North America 21 (1): 93–100. February 1994. doi:10.1016/S0094-0143(21)00597-8. PMID 7904388. 
  6. ↑ 6.0 6.1 "Osteoarthritis, genetic and molecular mechanisms". Biogerontology 3 (1–2): 85–88. 2002. doi:10.1023/a:1015219716583. PMID 12014849. 
  7. ↑ "Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study". JAMA Ophthalmology 137 (11): 1275–1282. November 2019. doi:10.1001/jamaophthalmol.2019.3392. PMID 31486843. 
  8. ↑ "Pentosan polysulfate" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/37720. 
  9. ↑ "Pentosan polysulfate" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/37720. 
  10. ↑ "Safety of Cartrophen Vet in the dog: review of adverse reaction reports in the UK". The Journal of Small Animal Practice 44 (5): 202–208. May 2003. doi:10.1111/j.1748-5827.2003.tb00144.x. PMID 12779171. 
  11. ↑ "Intra-articular therapy in osteoarthritis". Postgraduate Medical Journal 79 (934): 449–453. August 2003. doi:10.1136/pmj.79.934.449. PMID 12954956. 
  12. ↑ "The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment". Seminars in Arthritis and Rheumatism 28 (4): 211–267. February 1999. doi:10.1016/s0049-0172(99)80021-3. PMID 10073500. 
  13. ↑ "Comparison of the anti-prion mechanism of four different anti-prion compounds, anti-PrP monoclonal antibody 44B1, pentosan polysulfate, chlorpromazine, and U18666A, in prion-infected mouse neuroblastoma cells". PLOS ONE 9 (9): e106516. 2014. doi:10.1371/journal.pone.0106516. PMID 25181483. Bibcode: 2014PLoSO...9j6516Y. 
  14. ↑ "Characterizing antiprion compounds based on their binding properties to prion proteins: implications as medical chaperones". Protein Science 22 (1): 22–34. January 2013. doi:10.1002/pro.2180. PMID 23081827. 
  15. ↑ "Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease". Acta Neurochirurgica 148 (6): 677–9; discussion 679. June 2006. doi:10.1007/s00701-006-0772-y. PMID 16598408. 
  16. ↑ "Research will now assess CJD drug". 1 March 2005. http://news.bbc.co.uk/1/hi/health/4306351.stm. 
  17. ↑ "Systemic use of pentosan polysulphate in the treatment of osteoarthritis". The Journal of Small Animal Practice 37 (3): 108–114. March 1996. doi:10.1111/j.1748-5827.1996.tb02355.x. PMID 8683953. 
  18. ↑ "Vascular mechanisms in osteoarthritis". Best Practice & Research. Clinical Rheumatology 15 (5): 693–709. December 2001. doi:10.1053/berh.2001.0188. PMID 11812016. 
  19. ↑ "Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency". The Veterinary Record 146 (15): 433–437. April 2000. doi:10.1136/vr.146.15.433. PMID 10811265. 
  20. ↑ "Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial". Veterinary Surgery 36 (3): 234–244. April 2007. doi:10.1111/j.1532-950x.2007.00256.x. PMID 17461948. 
  21. ↑ 21.0 21.1 21.2 21.3 "FDA Approves First Injectable Pentosan for Osteoarthritis in Horses". 20 December 2022. https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-injectable-pentosan-osteoarthritis-horses.  This article incorporates text from this source, which is in the public domain.
  22. ↑ Joint Disease in the Horse. Philadelphia: WB Saunders Company. 1996. pp. 281–292. 
  23. ↑ "Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses". American Journal of Veterinary Research 73 (5): 628–633. May 2012. doi:10.2460/ajvr.73.5.628. PMID 22533393. 



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