Pentosan Polysulfate Sodium

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Structural formula
Structural formula of pentosan polysulfate
General
Surname Pentosan polysulfate
other names
  • BAY-946
  • HOE-946
  • Pentosan sulfur polyester
  • Polypentose sulfate
  • polysulfated xylan
  • PZ-68
  • SP-54
  • Xylan SP54
  • Xylan sulfate
CAS number
  • 37300-21-3 (free acid)
  • 116001-96-8 (sodium salt)
PubChem 37720
ATC code
DrugBank DB00686
properties
safety instructions
Please note the restricted labeling requirements for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no classification available
H and P phrases H: see above
P: see above
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

In pentosan-sodium , reduced pentosan (PPS) is, to a plant, synthesized from beech bark heparinoid . Chemically, pentosan polysulphate (PPS, (1 → 4) -β-xylan-2,3-bis (hydrogen sulphate) with a 4 O -methyl-α- D -glucuronate) is a semi-synthetic polysulphated xylan , i.e. a large molecule made of sugar molecules attached to one another ( Polysaccharide) with sulfur components. Pentosan polysulfate is used as a drug for the treatment of interstitial cystitis , thrombosis and osteoarthritis . Another use in veterinary medicine is the treatment of osteoarthritis in dogs and horses. According to the ATC code (B01AX05), the drug is assigned to the same class of anticoagulants as the fully synthetic pentasaccharide fondaparinux . The calcium salt of PPS was one of the first disease-modifying osteoarthritis drugs.

Clinical information

application areas

Pentosan polysulfate is used as a drug to treat interstitial cystitis. Another area of ​​application are thromboembolic diseases, e.g. B. the treatment of varicose veins and superficial thrombophlebitis, of post-thrombotic or post-traumatic edema , of hematomas after bruises and sprains and hemorrhoids.

Interstitial cystitis / chronic bladder pain syndrome

Interstitial cystitis / chronic bladder pain syndrome , English Bladder Pain Syndrome (IC / BPS), is a non-infectious chronic inflammation of the urinary bladder , caused by dysfunction / damage to the protective layer of the urothelium , the so-called glycosaminoglycan layer . Symptoms are frequent urination in small amounts ( pollakiuria ), frequent nocturnal urination ( nocturia ) and the need to urinate that is difficult to control (imperative), pressure and / or pain, painful sexual intercourse ( dyspareunia ), pain and / or discomfort when sitting. PPS is the only oral drug approved by the US Food and Drug Administration (FDA) for the treatment of IC / BPS since 1996. The drug is available under the name elmiron as capsules or for direct infusion into the bladder. The European Medicines Agency (EMA) approved the active ingredient pentosan polysulphate for the therapy of IC / BPS in October 2017. A review of four placebo-controlled studies concluded that PPS taken orally was significantly more effective than placebo on pain, urgency and frequency of urination, but that the effect of nocturnal toilet visits (nocturia) was no different from placebo.

Hemorrhagic cystitis after radiation therapy

Pentosan polysulfate has also been shown to be effective in treating hemorrhagic cystitis caused as a side effect of radiation therapy . Successes in the treatment of hemorrhagic cystitis in children after chemotherapy in connection with a stem cell transplant have also been reported.

Prostatitis

In patients suffering from chronic prostatitis or chronic pelvic pain syndrome, pentosan polysulfate, taken orally three times a day at a dose of 300 mg for a treatment period of 4 months, appears to lead to an improvement in pain symptoms.

Osteoarthritis

PPS was first mentioned as a chondroprotective drug in 1988. In 1999 a detailed justification for the disease-modifying activity of this molecule was published. The mechanism of PPS action in osteoarthritis has many factors. The focus is on both the stimulation of cartilage matrix synthesis and the prevention of cartilage degradation. There are also systemic effects on blood lipids and fibrinolysis that can help cleanse the subchondral circulation. Calcium pentosan polysulphate (CaPPS) was shown to be better absorbed than the sodium salt when taken orally. In experimentally inflamed rabbit joints, it maintained proteoglycan levels in the articular cartilage.

Contraindications

PPS should not be used in the event of hypersensitivity / allergy to sodium pentosan polysulphate or the active ingredient heparin . PPS is also contraindicated in the case of existing bleeding - does not apply to menstrual bleeding. In patients who are at risk of bleeding before an operation, if there are signs of a coagulation disorder, if there is an increased tendency to bleed due to other medications, in patients with a reduced number of blood platelets caused by heparin and patients with reduced liver or kidney function, the drug should only be taken after the risk-benefit assessment and Check by the doctor.

Drug interactions

Of the drugs with pentosan polysulfate available in Germany, no interactions with other drugs or active ingredients are known when taken orally.

unwanted effects

Side effects reported by patients who have taken PPS orally include gastrointestinal symptoms such as diarrhea, heartburn and stomach pain, hair loss, headache, rash and insomnia. Because of the anticoagulant effects of elmiron, some patients report bruising. Before performing any surgery, it should be checked to see if drug use is stopped to reduce the risk of bleeding. Since 2018, there have been various reports of maculopathy associated with impaired vision, a disease of the macula , the point of sharpest vision in the retina. The finding is dose-dependent: 11% of the patients with a total intake between 500 and 999 grams and 42% of the patients with an intake of more than 1500 grams showed the eye findings in a study in California.

Pharmacological properties

Mechanism of action

Mechanism of Action Interstitial Cystitis / Painful Bladder Syndrome

PPS is believed to work by creating a protective layer on the damaged bladder wall. In its structure, PPS is similar to the natural glycosaminoglycan coating on the inner surface of the bladder. By replacing or repairing these, their permeability is reduced. The coating prevents urine toxins from irritating the underlying cell layers. This mechanism was demonstrated by irritating the inner surface of the bladders of female rats with acrolein. When the rats were pretreated with PPS, the damage was much less. Potassium sensitivity tests (PST) showed abnormal cell feed permeability and a significant reduction in permeability after successful PPS therapy in most patients with IC. Another possible mechanism for the action of PPS in IC is to inhibit the inflammatory response of the bladder cells, either by indirectly blocking the activity of mediators such as NF-κB by preventing an influx of mast cells or by preventing the release of histamine by mast cells.

Absorption and distribution in the body

The sodium salt of PPS has little bioavailability when taken orally. Research presented by Alza Pharmaceuticals in 2005 showed that 94% of drugs were excreted in the stool, meaning 6% was excreted in the urine and in contact with the bladder. The drug seems to be most effective when taken for several months. Furthermore, PPS was investigated as part of a “rescue instillation”, which is placed directly in the bladder and which may be more effective. Research presented in 2005 showed that PPS was 90% effective in reducing symptoms in IC patients through this instillation.

Trade names

Brand names include elmiron (as the sodium salt), Hemoclar, Anarthron, Fibrase, Fibrocid, Thrombocid and SP54. PPS capsules are sold in India under the brand names Comfora, Pentossan-100, Cystopen and For-IC. In the veterinary sector, pentosan polysulphate is sold as Cartrophen Vet and Sylvet by Biopharm Australia, Pentosan by NaturVet Australia, Anarthron by Randlab Australia and Zydax by Parnell.

Web links

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ Wolfgang Löscher, Angelika Richter: Textbook of Pharmacology and Toxicology for Veterinary Medicine Stuttgart 2016, p. 202 f.
  3. ↑ Expert committee for prescription requirements: Votes of the expert committee for prescription requirements according to § 53 AMG - 61st meeting, 01.07.2008 - 8th pentosan polysulphate. (PDF) In: Federal Institute for Drugs and Medical Devices. July 1, 2008, accessed March 15, 2019 .
  4. ^ P Ghosh, M Smith: Osteoarthritis, genetic and molecular mechanisms . In: Biogerontology . 3, No. 1-2, 2002, pp. 85-88. doi : 10.1023 / a: 1015219716583 . PMID 12014849 .
  5. ↑ Draft Guidance for Industry on Bioequivalence Recommendations for Pentosan Polysulfate Sodium Capsule; Availability. In: federalregister.gov. September 20, 2012, accessed March 27, 2019 .
  6. ↑ Pentosan Polysulfate. In: sciencedirect.com. Retrieved March 27, 2019 .
  7. ↑ Thomas Meißner: Urologists bring "light into the dark" in interstitial cystitis. In: aerzteblatt.de. October 15, 2004, accessed March 19, 2019 .
  8. ↑ P Hwang, B Auclair, D Beechinor, M Diment, TR Einarson: Efficacy of pentosan polysulfate in the treatment of interstitial cystitis: a meta-analysis . In: Urology . 50, No. 1, July 1997, pp. 39-43. doi : 10.1016 / S0090-4295 (97) 00110-6 . PMID 9218016 .
  9. ↑ Parsons CL: Successful management of radiation cystitis with sodium pentosan polysulfate . In: J. Urol. tape 136 , no. 4 , October 1986, p. 813-814 , PMID 2428986 .
  10. ^ SG Smit, with CF Heyns: Management of radiation cystitis . In: Nat Rev Urol . tape 7 , no. 4 , April 2010, p. 206-214 , doi : 10.1038 / nrurol.2010.23 , PMID 20212517 .
  11. ↑ Hampson SJ with Woodhouse CR: Sodium pentosanpolysulphate in the management of haemorrhagic cystitis: experience with 14 patients . In: Eur. Urol. tape 25 , no. 1 , 1994, p. 40-42 , PMID 7508397 .
  12. ^ SS Sandhu, with M Goldstraw, CR Woodhouse: The management of haemorrhagic cystitis with sodium pentosan polysulphate . In: BJU Int. tape 94 , no. 6 , October 2004, p. 845-847 , doi : 10.1111 / j.1464-410X.2004.05044.x , PMID 15476520 .
  13. ↑ G Duthie, with L Whyte, H Chandran, S Lawson, M Velangi, L McCarthy: Introduction of sodium pentosan polysulfate and avoidance of urethral catheterisation: improved outcomes in children with haemorrhagic cystitis post stem cell transplant / chemotherapy . In: J. Pediatr. Surg. tape 47 , no. 2 , February 2012, p. 375-379 , doi : 10.1016 / j.jpedsurg.2011.11.037 , PMID 22325394 .
  14. ↑ JC Nickel, with B Johnston, J Downey, J Barkin, P Pommerville, M Gregoire, E Ramsey: Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): a prospective multicenter clinical trial . In: Urology . tape 56 , no. 3 , September 2000, pp. 413-417 , PMID 10962305 .
  15. ↑ JC Nickel, with JB Forrest, K Tomera, J Hernandez-Graulau, TD Moon, AJ Schaeffer, JN Krieger, SI Zeitlin, RJ Evans, DJ Lama, DENeal, GR Sant: Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome : a multicenter, randomized, placebo controlled study . In: J. Urol. tape 173 , no. 4 , April 2005, p. 1252-1255 , doi : 10.1097 / 01.ju.0000159198.83103.01 , PMID 15758763 .
  16. ↑ H Wedren: Effects of sodium pentosanpolysulphate on symptoms related to chronic non-bacterial prostatitis. A double-blind randomized study . In: Scand. J. Urol. Nephrol. tape 21 , no. 2 , 1987, pp. 81-88 , PMID 2441458 .
  17. ^ RD Altman, P Kapila, DD Dean, DS Howell: Future therapeutic trends in osteoarthritis . In: Scand J Rheumatol . 77, No. Suppl, 1988, pp. 37-42. doi : 10.3109 / 03009748809096934 . PMID 3070732 .
  18. ↑ P Ghosh: The pathobiology of osteoarthritis and the rationale for the use of pentosan polysulfate for its treatment . In: Semin Arthritis Rheum . 28, No. 4, 1999, pp. 211-267. doi : 10.1016 / s0049-0172 (99) 80021-3 . PMID 10073500 .
  19. ↑ HP Klocking, J Hauptmann, M Richter: Profibrinolytic and anticoagulant properties of the pentosan polysulphate derivative bego 0391 . In: Pharmacy . 46, 1991, pp. 543-544. PMID 1723804 .
  20. ↑ MM Smith, P Ghosh, Y Numata, M Bansal: The effects of orally administered calcium pentosan polysulfate on inflammation and cartilage degradation produced in rabbit joints by intraarticular injection of a hyaluronate-polylysine complex . In: Arthritis Rheum . 37, No. 1, 1994, pp. 125-136. doi : 10.1002 / art.1780370118 . PMID 7510481 .
  21. ↑ Andrea Lubliner: Sodium Pentosan Polysulfate. In: onmeda.de. October 23, 2017. Retrieved March 27, 2019 .
  22. ↑ Andrea Lubliner: Sodium Pentosan Polysulfate. In: onmeda.de. October 23, 2017. Retrieved March 27, 2019 .
  23. ↑ Reviews - Pentosan Polysulfate Sodium Side Effects. Retrieved March 15, 2019 .
  24. ↑ Pentosan Polysulfate . In: MedlinePlus . National Institutes of Health. Retrieved April 4, 2019.
  25. ^ WA Pearce et al .: Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium . In: Ophthalmology , 2018, 125, pp. 1793-1802.
  26. ↑ Lecture Robin Vora: Prevalence of Maculopathy associated with Pentosan Polysulfate Therapy in Kaiser Permanente Northern California. American Academy of Ophthalmology (AAO) meeting in San Francisco, October 12, 2019.
  27. ^ CL Parsons: The therapeutic role of sulfated polysaccharides in the urinary bladder . In: Urol Clin North Am . 21, No. 1, 1994, pp. 93-100. PMID 7904388 .
  28. ↑ SJ Kalota, PC Stein, CL Parsons: Prevention of acrolein-induced bladder injury by pentosanpolysulfate . In: J Urol . 148, No. 1, 1992, pp. 163-166. doi : 10.1016 / s0022-5347 (17) 36545-x . PMID 1377288 .
  29. ↑ CL Parsons, J Forrest, JC Nickel, R Evans, LK Lloyd, J Barkin, PG Mosbaugh, DM Kaufman, JM Hernandez-Graulau, L Atkinson, D Albrecht: Effect of pentosan polysulfate therapy on intravesical potassium sensitivity . In: Urology . 59, No. 3, 2002, pp. 329-333. doi : 10.1016 / s0090-4295 (01) 01586-2 . PMID 11880064 .
  30. ↑ PC Sadhukhan, MB Tchetgen, RR Rackley, SP Vasavada, L Liou, SK Bandyopadhyay: Sodium pentosan polysulfate reduces urothelial responses to inflammatory stimuli via an indirect mechanism . In: J Urol . 168, No. 1, 2002, pp. 289-292. doi : 10.1016 / s0022-5347 (05) 64909-9 . PMID 12050558 .
  31. ↑ G Chiang, P Patra, R Letourneau, S Jeudy, W Boucher, M Green, GR Sant, TC Theoharides: Pentosanpolysulfate inhibits mast cell histamine secretion and intracellular calcium ion levels: an alternative explanation of its beneficial effect in interstitial cystitis . In: J Urol . 164, No. 6, 2002, pp. 2119-2125. doi : 10.1016 / s0022-5347 (05) 66981-9 . PMID 11061939 .
  32. ↑ G Chiang, P Patra, R Letourneau, S Jeudy, W Boucher, M Green, GR Sant, TC Theoharides: Pentosanpolysulfate (Elmiron) is a potent inhibitor of mast cell histamine secretion . In: Adv Exp Med Biol . 539, No. Pt B, 2003, pp. 713-729. PMID 15176320 .
  33. ^ M Simon, RH McClanahan, JF Shah: Metabolism of [3H] pentosan polysulfate sodium (PPS) in healthy human volunteers . In: Xenobiotica . 35, No. 8, August 2005, pp. 775-84. doi : 10.1080 / 00498250500230586 . PMID 16278190 .
  34. ↑ C Parsons: Successful downregulation of bladder sensory nerves with combination of heparin and alkalinized lidocaine in patients with interstitial cystitis . In: Urology . 65, No. 1, 2005, pp. 45-48. doi : 10.1016 / j.urology.2004.08.056 . PMID pmid15667861.