Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Pentosan polysulfate: Difference between pages

{{Short description|Chemical compound}}

{{Use dmy dates|date=May 2023}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 464198430

| width = 150

| alt =

| caption =

<!-- Clinical data -->

| pronounce =

| tradename = Elmiron, Zycosan

| Drugs.com = {{drugs.com|monograph|pentosan}}

| MedlinePlus =

| licence_CA = <!-- Health Canada may use generic or brand name (generic name preferred) -->

| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->

| DailyMedID = pentosan polysulfate

| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->

| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[By mouth]], [[intramuscular injection|intramuscular]]

| class =

| ATCvet =

| ATC_prefix = C05

| ATC_suffix = BA04

| ATC_supplemental = {{ATC|G04|BX15}}, {{ATCvet|C05|BA04}}, {{ATCvet|G04|BX15}} {{ATCvet|M01|AX90}}

<!-- Legal status -->

| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref name="Elmiron FDA label">{{cite web | title=Elmiron- pentosan polysulfate sodium capsule, gelatin coated | website=DailyMed | date=10 November 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0ba651e-3d8a-11df-8fbe-119855d89593 | access-date=21 December 2022}}</ref>

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion = Feces, urine<ref name="Elmiron FDA label" />

<!-- Identifiers -->

| index2_label = as sodium

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 140207-93-8

| IUPHAR_ligand =

| DrugBank = DB00686

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 34595

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = F59P8B75R4

| UNII2 = 914032762Y

| KEGG2 = D05428

| ChEBI =

| ChEMBL = 4073796

| ChEMBL2 = 1201516

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = PPS, (1->4)-β-Xylan 2,3-bis(hydrogen sulfate) with a 4 O-methyl-α-D-glucuronate

<!-- Chemical and physical data -->

| IUPAC_name =

| C = 10 | H = 18 | O = 21 | S = 4

| SMILES = O[C@@H]1CO[C@@H](O[C@@H]2CO[C@@H](O)[C@H](OS(O)(=O)=O)[C@H]2OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O

| StdInChI = 1S/C10H18O21S4/c11-3-1-26-10(8(31-35(22,23)24)5(3)28-32(13,14)15)27-4-2-25-9(12)7(30-34(19,20)21)6(4)29-33(16,17)18/h3-12H,1-2H2,(H,13,14,15)(H,16,17,18)(H,19,20,21)(H,22,23,24)/t3-,4-,5+,6+,7-,8-,9-,10+/m1/s1

| StdInChI_comment =

| StdInChIKey = FCCNSUIJIOOXEZ-SJYYZXOBSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

'''Pentosan polysulfate''', sold under the brand name '''Elmiron''' among others, is a [[medication]] used for the treatment of [[interstitial cystitis]].<ref name="Elmiron FDA label" /> It was approved for medical use in the United States in 1996.<ref name="Elmiron FDA label" /><ref name=pmid34000253>{{cite journal | vauthors = Lindeke-Myers A, Hanif AM, Jain N | title = Pentosan polysulfate maculopathy | journal = Survey of Ophthalmology | volume = 67 | issue = 1 | pages = 83–96 | date = 2022 | pmid = 34000253 | doi = 10.1016/j.survophthal.2021.05.005 | s2cid = 234767956 | doi-access = free }}</ref><ref>{{cite web | title = Elmiron (pentosan polysulfate sodium) | work = FDA approval letter | publisher = U.S. Food and Drug Administration | date = 25 September 1996 | url = https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020193Orig1s000rev.pdf}}</ref>

==Medical uses==

Pentosan polysulfate sodium is [[indicated]] for the relief of bladder pain or discomfort associated with interstitial cystitis.<ref name="Elmiron FDA label" />

==Adverse effects==

Patients who have taken pentosan polysulfate orally report a variety of side effects, primarily [[gastrointestinal complaint]]s such as [[diarrhea]], [[heartburn]], and stomach pain.<ref name="side effects">{{cite web|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0045790/ |title=Pentosan Polysulfate |author=Pubmed Health |year=2012 |publisher=U.S. National Library of Medicine |access-date=2 October 2012}}</ref> [[Alopecia|Hair loss]], [[headache]], [[rash]], and [[insomnia]] have also been reported.<ref name="side effects"/> 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 [[retina]]l toxicity, mimicking pigmentary pattern dystrophy.<ref name=pmid34000253/><ref name=pmid7904388/><ref name=pmid12014849/><ref>{{cite journal | vauthors = Hanif AM, Armenti ST, Taylor SC, Shah RA, Igelman AD, Jayasundera KT, Pennesi ME, Khurana RN, Foote JE, O'Keefe GA, Yang P, Hubbard GB, Hwang TS, Flaxel CJ, Stein JD, Yan J, Jain N | display-authors = 6 | title = Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study | journal = JAMA Ophthalmology | volume = 137 | issue = 11 | pages = 1275–1282 | date = November 2019 | pmid = 31486843 | pmc = 6735406 | doi = 10.1001/jamaophthalmol.2019.3392 }}</ref>

==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 [[wikt:permeable|permeability]].<ref name=pmid7904388>{{cite journal | vauthors = Parsons CL | title = The therapeutic role of sulfated polysaccharides in the urinary bladder | journal = The Urologic Clinics of North America | volume = 21 | issue = 1 | pages = 93–100 | date = February 1994 | pmid = 7904388 | doi = 10.1016/S0094-0143(21)00597-8 }}</ref>

==History==

The calcium salt of pentosan polysulfate was one of the first reported disease-modifying osteoarthritis drugs (DMOAD).<ref name=pmid12014849>{{cite journal | vauthors = Ghosh P, Smith M | title = Osteoarthritis, genetic and molecular mechanisms | journal = Biogerontology | volume = 3 | issue = 1–2 | pages = 85–88 | date = 2002 | pmid = 12014849 | doi = 10.1023/a:1015219716583 | s2cid = 33755966 }}</ref>

== 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.<ref>{{Cite web | work = PubChem | publisher = U.S. National Library of Medicine |title=Pentosan polysulfate |url=https://pubchem.ncbi.nlm.nih.gov/compound/37720 |access-date=8 November 2022 |language=en}}</ref>

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.<ref>{{Cite web | work = PubChem | publisher = U.S. National Library of Medicine |title=Pentosan polysulfate |url=https://pubchem.ncbi.nlm.nih.gov/compound/37720 |access-date=8 November 2022 |language=en}}</ref>

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.<ref>{{cite journal | vauthors = Hannon RL, Smith JG, Cullis-Hill D, Ghosh P, Cawdery MJ | title = Safety of Cartrophen Vet in the dog: review of adverse reaction reports in the UK | journal = The Journal of Small Animal Practice | volume = 44 | issue = 5 | pages = 202–208 | date = May 2003 | pmid = 12779171 | doi = 10.1111/j.1748-5827.2003.tb00144.x }}</ref>

==Research==

===Osteoarthritis===

Pentosan polysulfate has been studied in knee [[osteoarthritis]], though evidence to support such use is poor as of 2003.<ref>{{cite journal | vauthors = Uthman I, Raynauld JP, Haraoui B | title = Intra-articular therapy in osteoarthritis | journal = Postgraduate Medical Journal | volume = 79 | issue = 934 | pages = 449–453 | date = August 2003 | pmid = 12954956 | pmc = 1742771 | doi = 10.1136/pmj.79.934.449 }}</ref> There is some theoretical evidence that it should help.<ref name=ghosh99>{{cite journal | vauthors = Ghosh P | title = The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment | journal = Seminars in Arthritis and Rheumatism | volume = 28 | issue = 4 | pages = 211–267 | date = February 1999 | pmid = 10073500 | doi = 10.1016/s0049-0172(99)80021-3 }}</ref>

===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.<ref>{{cite journal | vauthors = Yamasaki T, Suzuki A, Hasebe R, Horiuchi M | title = 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 | journal = PLOS ONE | volume = 9 | issue = 9 | pages = e106516 | date = 2014 | pmid = 25181483 | pmc = 4152300 | doi = 10.1371/journal.pone.0106516 | bibcode = 2014PLoSO...9j6516Y | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Kamatari YO, Hayano Y, Yamaguchi K, Hosokawa-Muto J, Kuwata K | title = Characterizing antiprion compounds based on their binding properties to prion proteins: implications as medical chaperones | journal = Protein Science | volume = 22 | issue = 1 | pages = 22–34 | date = January 2013 | pmid = 23081827 | pmc = 3575857 | doi = 10.1002/pro.2180 }}</ref>

The treatment<ref>{{cite journal | vauthors = Whittle IR, Knight RS, Will RG | title = Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt-Jakob disease | journal = Acta Neurochirurgica | volume = 148 | issue = 6 | pages = 677–9; discussion 679 | date = June 2006 | pmid = 16598408 | doi = 10.1007/s00701-006-0772-y | s2cid = 37400744 }}</ref> of [[Jonathan Simms|one patient in Northern Ireland]] and around six other patients in mainland Britain was reported in the press.<ref>{{Cite news|url=http://news.bbc.co.uk/1/hi/health/4306351.stm|title=Research will now assess CJD drug|date=1 March 2005|via=news.bbc.co.uk}}</ref>

==Veterinary uses==

===Dogs===

Read et al. (1996) <ref>{{cite journal | vauthors = Read RA, Cullis-Hill D, Jones MP | title = Systemic use of pentosan polysulphate in the treatment of osteoarthritis | journal = The Journal of Small Animal Practice | volume = 37 | issue = 3 | pages = 108–114 | date = March 1996 | pmid = 8683953 | doi = 10.1111/j.1748-5827.1996.tb02355.x }}</ref> 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&nbsp;mg/kg dose was the most effective. In a study conducted with 10 elderly dogs with osteoarthritis given calcium pentosan polysulfate (3&nbsp;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.<ref>{{cite journal | vauthors = Ghosh P, Cheras PA | title = Vascular mechanisms in osteoarthritis | journal = Best Practice & Research. Clinical Rheumatology | volume = 15 | issue = 5 | pages = 693–709 | date = December 2001 | pmid = 11812016 | doi = 10.1053/berh.2001.0188 }}</ref> 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.<ref>{{cite journal | vauthors = Innes JF, Barr AR, Sharif M | title = Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency | journal = The Veterinary Record | volume = 146 | issue = 15 | pages = 433–437 | date = April 2000 | pmid = 10811265 | doi = 10.1136/vr.146.15.433 | s2cid = 46623547 }}</ref> The efficacy of subcutaneous sodium pentosan polysulfate (3&nbsp;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 force]]s, over 48 weeks.<ref>{{cite journal | vauthors = Budsberg SC, Bergh MS, Reynolds LR, Streppa HK | title = Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial | journal = Veterinary Surgery | volume = 36 | issue = 3 | pages = 234–244 | date = April 2007 | pmid = 17461948 | doi = 10.1111/j.1532-950x.2007.00256.x }}</ref>

===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).<ref name="FDA Zycosan" />

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.<ref name="FDA Zycosan">{{cite web | title=FDA Approves First Injectable Pentosan for Osteoarthritis in Horses | website=U.S. [[Food and Drug Administration]] (FDA) | date=20 December 2022 | url=https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-injectable-pentosan-osteoarthritis-horses | access-date=21 December 2022}} {{PD-notice}}</ref> Zycosan is for intramuscular use in horses only and is not for use in humans.<ref name="FDA Zycosan" /> Zycosan is sponsored by Anzac Animal Health LLC, based in Maryland Heights, Missouri.<ref name="FDA Zycosan" />

Pentosan polysulfate is being used for this osteoarthritis in Australia. When administered to racing thoroughbreds with chronic osteoarthritis (2 to 3&nbsp;mg/kg, intramuscularly, once weekly for 4 weeks, then as required), pentosan polysulfate treatment improved but did not eliminate clinical signs of joint disease.<ref>{{cite book| vauthors = Little CB, Ghosh P | veditors = McIlwraith CW, Trotter GW |title=Joint Disease in the Horse|date=1996|publisher=WB Saunders Company|location=Philadelphia|pages=281–292}}</ref> Articular cartilage fibrillation was substantially reduced by similar NaPPS treatment intramuscularly in nine horses with experimentally-induced carpal osteoarthritis.<ref>{{cite journal | vauthors = McIlwraith CW, Frisbie DD, Kawcak CE | title = Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses | journal = American Journal of Veterinary Research | volume = 73 | issue = 5 | pages = 628–633 | date = May 2012 | pmid = 22533393 | doi = 10.2460/ajvr.73.5.628 | doi-access = free }}</ref>

== References ==

{{Reflist}}

{{Vasoprotectives}}

{{Urologicals, including antispasmodics}}

{{Portal bar | Medicine}}

{{DEFAULTSORT:Pentosan Polysulfate}}

[[Category:Drugs acting on the musculoskeletal system]]

[[Category:Urologic pelvic pain syndrome]]

[[Category:IARC Group 2B carcinogens]]