Pentosan polysulfate

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Pentosan polysulfate
Pentosan polysulfate.svg
Clinical data
Trade names Elmiron, Zycosan
Other namesPPS, (1->4)-β-Xylan 2,3-bis(hydrogen sulfate) with a 4 O-methyl-α-D-glucuronate
AHFS/Drugs.com Monograph
License data
Routes of
administration 		By mouth, intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
Excretion Feces, urine [1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H18O21S4
Molar mass 602.47 g·mol−1
3D model (JSmol)
  • 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
  • InChI=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
  • Key:FCCNSUIJIOOXEZ-SJYYZXOBSA-N
   (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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Creutzfeldt–Jakob disease</span> Degenerative neurological disorder

Creutzfeldt–Jakob disease (CJD), also known as subacute spongiform encephalopathy or neurocognitive disorder due to prion disease, is an invariably fatal degenerative brain disorder. Early symptoms include memory problems, behavioral changes, poor coordination, and visual disturbances. Later symptoms include dementia, involuntary movements, blindness, weakness, and coma. About 70% of people die within a year of diagnosis. The name Creutzfeldt–Jakob disease was introduced by Walther Spielmeyer in 1922, after the German neurologists Hans Gerhard Creutzfeldt and Alfons Maria Jakob.

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

Interstitial cystitis (IC), a type of bladder pain syndrome (BPS), is chronic pain in the bladder and pelvic floor of unknown cause. It is the urologic chronic pelvic pain syndrome of women. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and fibromyalgia.

<span class="mw-page-title-main">Chondroitin sulfate</span> Sulfated glycosaminoglycan (GAG) compound

Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of a chain of alternating sugars. It is usually found attached to proteins as part of a proteoglycan. A chondroitin chain can have over 100 individual sugars, each of which can be sulfated in variable positions and quantities. Chondroitin sulfate is an important structural component of cartilage, and provides much of its resistance to compression. Along with glucosamine, chondroitin sulfate has become a widely used dietary supplement for treatment of osteoarthritis, although large clinical trials failed to demonstrate any symptomatic benefit of chondroitin.

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

Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible to MH are generally unaffected when not exposed to triggering agents.

Glucosamine (C6H13NO5) is an amino sugar and a prominent precursor in the biochemical synthesis of glycosylated proteins and lipids. Glucosamine is part of the structure of two polysaccharides, chitosan and chitin. Glucosamine is one of the most abundant monosaccharides. Produced commercially by the hydrolysis of shellfish exoskeletons or, less commonly, by fermentation of a grain such as corn or wheat, glucosamine has many names depending on country.

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

Nimodipine, sold under the brand name Nimotop among others, is calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage. It was originally developed within the calcium channel blocker class as it was used for the treatment of high blood pressure, but is not used for this indication.

<span class="mw-page-title-main">Carprofen</span> Non-steroidal anti-inflammatory drug

Carprofen is a non-steroidal anti-inflammatory drug (NSAID) of the carbazole and propionic acid class that was previously for use in humans and animals, but is now only available to veterinarians for prescribing as a supportive treatment for various conditions in only animals. Carprofen reduces inflammation by inhibition of COX-1 and COX-2; its specificity for COX-2 varies from species to species. Marketed under many brand names worldwide, carprofen provides day-to-day treatment for pain and inflammation from various kinds of joint pain, as well as post-operative pain.

<span class="mw-page-title-main">Feline lower urinary tract disease</span> Any disorder affecting the bladder or urethra of cats

Feline lower urinary tract disease (FLUTD) is a generic category term to describe any disorder affecting the bladder or urethra of cats.

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

Calcium gluconate is the calcium salt of gluconic acid and is used as a mineral supplement and medication. As a medication it is used by injection into a vein to treat low blood calcium, high blood potassium, and magnesium toxicity. Supplementation is generally only required when there is not enough calcium in the diet. Supplementation may be done to treat or prevent osteoporosis or rickets. It can also be taken by mouth but is not recommended for injection into a muscle.

Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. This second mechanism of action makes naproxcinod the first in a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects.

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

Ipodate sodium is an iodine-containing radiopaque contrast media used for X-rays. The drug is given orally and the resulting contrast allows for easy resolution of the bile duct and gall bladder.

Pentosans are polymers composed of pentoses. In contrast to cellulose, which is composed of hexose (glucose) monomers, pentosans are derived from five-carbon sugars such as xylose. Pentosan-rich biomass is the precursor to furfural.

Tanezumab is a monoclonal antibody against nerve growth factor as a treatment for pain via a novel mechanisms different from conventional pain-killer drugs. Tanezumab was discovered and developed by Rinat Neuroscience and was acquired by Pfizer in 2006.

Capillaria plica is a parasitic nematode which is most often found in the urinary bladder, and occasionally in the kidneys, of dogs and foxes. It has also been found in the domestic cat, and various wild mammals. Its presence usually produces no clinical symptoms, but in some cases, it leads to hematuria, cystitis, or difficulty in urination.

Feline idiopathic cystitis (FIC) or feline interstitial cystitis or cystitis in cats, is one of the most frequently observed forms of feline lower urinary tract disease (FLUTD). Feline cystitis means "inflammation of the bladder in cats". The term idiopathic means unknown cause; however, certain behaviours have been known to aggravate the illness once it has been initiated. It can affect both males and females of any breed of cat. It is more commonly found in female cats; however, when males do exhibit cystitis, it is usually more dangerous.

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

Sodium hyaluronate is the sodium salt of hyaluronic acid, a glycosaminoglycan found in various connective tissue of humans.

Adelmidrol is an anti-inflammatory ethanolamide derivative of azelaic acid.

The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally, systemically, or intralesionally, and the strategy for treatment may change as healing progresses. The end goal is to reduce the pain and inflammation associated with injury, to encourage the injured tissue to heal with normal structure and function, and to ultimately return the horse to the highest level of performance possible following recovery.

<span class="mw-page-title-main">Polysulfated glycosaminoglycan</span> Injectable drug

Polysulfated glycosaminoglycan (PSGAG), sold under the brand name Adequan, is an injectable drug for dogs and horses that is used to alleviate the limpness, pain, and lowered range of motion caused by arthritis. It is made of repeat disaccharide units (comprising hexosamine and hexuronic acid), and is similar to glycosaminoglycans already present in the cartilage; PSGAG thus easily integrates itself there. In vitro studies have shown it to inhibit the enzymes that degrade cartilage and bone, as well as suppress inflammation and stimulate the synthesis of replacement cartilage. While it can cause an increased risk of bleeding, it is relatively safe and has a high LD50. PSGAG is one of the most widely prescribed joint treatments for horses.

A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression of osteoarthritis. Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss of cartilage and potentially regenerate it. Other DMOADs may attempt to help repair adjacent tissues by reducing inflammation. A successful DMOAD would be expected to show an improvement in patient pain and function with an improvement of the health of the joint tissues.

References

  1. 1 2 3 4 5 "Elmiron- pentosan polysulfate sodium capsule, gelatin coated". DailyMed. 10 November 2022. Retrieved 21 December 2022.
  2. 1 2 Lindeke-Myers A, Hanif AM, Jain N (2022). "Pentosan polysulfate maculopathy". Survey of Ophthalmology . 67 (1): 83–96. doi:10.1016/j.survophthal.2021.05.005. PMID   34000253. S2CID   234767956.
  3. ↑ https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020193Orig1s000rev.pdf [ bare URL PDF ]
  4. 1 2 Pubmed Health (2012). "Pentosan Polysulfate". U.S. National Library of Medicine. Retrieved 2 October 2012.
  5. 1 2 Parsons CL (1994). "The therapeutic role of sulfated polysaccharides in the urinary bladder". Urol Clin North Am. 21 (1): 93–100. doi:10.1016/S0094-0143(21)00597-8. PMID   7904388.
  6. 1 2 Ghosh, P; Smith, M (2002). "Osteoarthritis, genetic and molecular mechanisms". Biogerontology. 3 (1–2): 85–8. doi:10.1023/a:1015219716583. PMID   12014849. S2CID   33755966.
  7. ↑ Hanif AM, Armenti ST, Taylor SC, Shah RA, Igelman AD, Jayasundera KT, et al. (November 2019). "Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study". JAMA Ophthalmology. 137 (11): 1275–1282. doi:10.1001/jamaophthalmol.2019.3392. PMC   6735406 . PMID   31486843.
  8. ↑ PubChem. "Pentosan polysulfate". pubchem.ncbi.nlm.nih.gov. Retrieved 8 November 2022.
  9. ↑ PubChem. "Pentosan polysulfate". pubchem.ncbi.nlm.nih.gov. Retrieved 8 November 2022.
  10. ↑ Hannon, R. L.; Smith, J. G.; Cullis-Hill, D.; Ghosh, P.; Cawdery, M. J. Hope (2003). "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. doi:10.1111/j.1748-5827.2003.tb00144.x. ISSN   0022-4510. PMID   12779171.
  11. ↑ Uthman I, Raynauld JP, Haraoui B (August 2003). "Intra-articular therapy in osteoarthritis". Postgraduate Medical Journal. 79 (934): 449–53. doi:10.1136/pmj.79.934.449. PMC   1742771 . PMID   12954956.
  12. ↑ Ghosh, P (1999). "The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment". Semin Arthritis Rheum. 28 (4): 211–67. doi:10.1016/s0049-0172(99)80021-3. PMID   10073500.
  13. ↑ Yamasaki, Takeshi; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro (2014). "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. Bibcode:2014PLoSO...9j6516Y. doi: 10.1371/journal.pone.0106516 . PMC   4152300 . PMID   25181483.
  14. ↑ Kamatari, Yuji O; Hayano, Yosake; Yamaguchi, Kei-ichi; Hosokawa-Muto, Junji; Kuwata, Kazuo (2012). "Characterizing antiprion compounds based on their binding properties to prion proteins: Implications as medical chaperones". Protein Sci. 22 (1): 22–34. doi:10.1002/pro.2180. PMC   3575857 . PMID   23081827.
  15. ↑ Whittle, IR; Knight, RS; Will, RG (2006). "Unsuccessful intraventricular pentosan polysulphate treatment of variant Creutzfeldt–Jakob disease". Acta Neurochir (Wien). 148 (6): 677–679. doi:10.1007/s00701-006-0772-y. PMID   16598408. S2CID   37400744.
  16. ↑ "Research will now assess CJD drug". 1 March 2005 – via news.bbc.co.uk.
  17. ↑ Read, RA; Cullis-Hill, D; Jones, MP (1996). "Systemic use of pentosan polysulphate in the treatment of osteoarthritis". J Small Anim Pract. 37 (3): 108–114. doi:10.1111/j.1748-5827.1996.tb02355.x. PMID   8683953.
  18. ↑ Ghosh, P; Cheras, PA (2001). "Vascular mechanisms in osteoarthritis". Best Pract Res Clin Rheumatol. 15 (5): 693–709. doi:10.1053/berh.2001.0188. PMID   11812016.
  19. ↑ Innes, JF; Barr, AR; Sharif, M (2000). "Efficacy of oral calcium pentosan polysulphate for the treatment of osteoarthritis of the canine stifle joint secondary to cranial cruciate ligament deficiency". Vet Rec. 146 (15): 433–437. doi:10.1136/vr.146.15.433. PMID   10811265. S2CID   46623547.
  20. ↑ Budsberg, SC; Bergh, MS; Reynolds, LR; Streppa, HK (2007). "Evaluation of pentosan polysulfate sodium in the postoperative recovery from cranial cruciate injury in dogs: a randomized, placebo-controlled clinical trial". Vet Surg. 36 (3): 234–244. doi:10.1111/j.1532-950x.2007.00256.x. PMID   17461948.
  21. 1 2 3 4 "FDA Approves First Injectable Pentosan for Osteoarthritis in Horses". U.S. Food and Drug Administration (FDA). 20 December 2022. Retrieved 21 December 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  22. ↑ Little, CB; Ghosh, P (1996). McIlwraith, CW; Trotter, GW (eds.). Joint Disease in the Horse. Philadelphia: WB Saunders Company. pp. 281–292.
  23. ↑ McIlwraith, CW; Frisbie, DD; Kawcak, CE (2012). "Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses". Am J Vet Res. 73 (5): 628–633. doi:10.2460/ajvr.73.5.628. PMID   22533393.
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