HIV-1

It has been demonstrated that pentosan polysulfate sodium inhibits HIV-1 activity in MT-4 cells, with an ED50 of 0.19 μg/mL. Complete suppression of HIV-1 antigen expression is achieved at a dose of 4.0 μg/mL. It suppresses HIV-1 antigen expression in HUT-78 cells with an ED50 of 0.02 μg/mL[2]. Pentosan Polysulfate Sodium inhibits TNFα's proinflammatory effects, suppresses NF-κB, and reduces the generation of MCP-1 induced by high glucose and advanced glycation end products (AGEs)[3].

In 5/6 nephrectomized rats, pentosan polysulfate sodium has been demonstrated to reduce glomerulosclerosis and interstitial inflammation. Treatment with pentosan polysulfate preserves renal function, lowers albuminuria considerably, and lessens renal lesions, especially tubulointerstitial inflammation, greatly. In aged diabetic kidneys, pentosan polysulfate sodium also decreases proinflammatory gene expression and TNFα upregulation[3].

Absorption, Distribution and Excretion
Sprague-Dawley rats were administered (orally or intravenously) 5 mg/kg body weight of (3)H-labeled pentosan and sacrificed 1 hour or 4 hours later. Autoradiography showed that after intravenous injection, the radiolabeled pentosan was widely distributed throughout the animal, with significant marking in connective tissue, while radioactivity was lower in bone and cartilage. The concentration of the radiolabeled pentosan in urine was high, and it preferentially localized to the lining of the urinary tract. After oral administration, the tissue distribution of the radiolabeled pentosan was similar, but the radioactivity was lower. After oral administration of 1.0–1.2 mg pentosan to rabbits, the median urinary recovery rate of low molecular weight pentosan was 7.45% (range: 2.1–46.0%), and the median urinary recovery rate of high molecular weight pentosan was 0.1% (range: 0.0–0.3%). Following intravenous administration of 1–1.2 mg pentosans to rabbits, the median recovery rate of unfractionated pentosans in urine was 47.2% (range: 19.7–73.2%), the recovery rate of low molecular weight pentosans was 74.6% (range: 31.4–96.3%), and the recovery rate of high molecular weight pentosans was 3.3% (range: 2.5–5.0%). A study investigated pentosan excretion in 34 female patients with interstitial cystitis who received long-term pentosan therapy. The median concentration of pentosans in the urine of these patients was 1.2 μg/mL (range: 0.5–27.7 μg/mL). All pentosans recovered from the urine of these patients were low molecular weight pentosans. For more complete data on the absorption, distribution, and excretion of Elmiron (12 in total), please visit the HSDB records page.

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Metabolism / Metabolites
Orally absorbed pentosan sodium sulfate undergoes partial desulfurization in the liver and spleen, and partial depolymerization in the kidneys, generating various metabolites. Continuous administration leads to saturation of both desulfurization and depolymerization pathways. (The repetition of the first paragraph is likely an error in the original text.)

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Biological Half-Life
Five healthy male volunteers received intravenous injections of 0.1, 1, 7, or 50 mg of (125)I-labeled pentosan and unlabeled pentosan, respectively. The half-life was 13–18 minutes for the 0.1–7 mg dose groups and 45 minutes for the 50 mg dose group. …After oral administration of 300 mg or 450 mg of radiolabeled pentosan sodium polysulfate solution, the mean plasma radioactivity half-lives were 27 hours and 20 hours, respectively.

Toxicity Summary
Identification and Uses: Elmiron (pentosyl sulfate) is a white powder. Elmiron is a weak anticoagulant (1/15 the activity of heparin). It is indicated for the relief of bladder pain or discomfort caused by interstitial cystitis. It is also used in veterinary medicine. Human Studies: Elmiron is a highly sulfated semi-synthetic pentosyl polysaccharide with properties similar to heparin, used to treat interstitial cystitis. There have been no reports of Elmiron overdose. Based on the pharmacodynamics of the drug, toxicity may manifest as anticoagulation, bleeding, thrombocytopenia, abnormal liver function, and gastrointestinal upset. Cases of severe thrombocytopenia and ischemic stroke following Elmiron treatment have been reported. Thrombocytopenia was reported in all 25 patients treated with heparin or Elmiron over a 7-month period. Based on platelet aggregation studies, it is suggested that the anticoagulant may cause an immune allergic reaction. Animal Studies: Elmiron was administered by gavage once daily, 5 days a week, for 2 years. Mice were given doses of 56, 168, or 504 mg/kg. Male rats were administered doses of 14, 42, or 126 mg/kg, and female rats were administered doses of 28, 84, or 252 mg/kg. Elmiron is carcinogenic in mice but not in rats. Increased incidence of hepatic angiosarcoma, hepatocellular tumors (primarily adenomas), and malignant lymphomas in female mice suggests that Elmiron has carcinogenic activity. Reproductive studies have been conducted in mice and rats at a daily intravenous dose of 15 mg/kg; and in rabbits at a daily intravenous dose of 7.5 mg/kg. These studies did not find evidence that Elmiron impairs fertility or harms the fetus. In the mouse micronucleus test or the Ames test (Salmonella typhimurium), sodium Elmiron did not show chromosomal breakage or mutagenicity.

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Interactions
This study investigated the effects of pentosan sulfate sodium on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Warfarin doses were titrated to an international normalized ratio (INR) of 1.4–1.8. Subjects continued to receive the titrated dose of warfarin and 100 mg of pentosan sulfate sodium or placebo every 8 hours for 7 days. The peak plasma concentrations (Cmax) of R-warfarin and S-warfarin were approximately 840–890 ng/mL and 680–730 ng/mL, respectively, and were similar in the presence or absence of pentosan sulfate sodium. The half-lives of R-warfarin and S-warfarin were 52–56 hours and 36–40 hours, respectively. There were no significant differences in prothrombin time, partial thromboplastin time, and INR between the warfarin + placebo group and the warfarin + pentosan sulfate sodium group. The AUC(INR) showed no therapeutic effect (P = 0.772); however, a cyclical effect was observed. Analysis of variance for treatment cycles showed no therapeutic effect (P > 0.1). Adverse events were mild, including headache, epistaxis, and rash. Most adverse events were treatment-independent and occurred during warfarin dose adjustments. Sodium pentosan sulfate does not affect the pharmacokinetics or pharmacodynamics of warfarin. The risk of bleeding may increase when sodium pentosan sulfate is used in combination with drugs that affect hemostasis (e.g., oral anticoagulants, heparin, nonsteroidal anti-inflammatory drugs (NSAIDs), thrombolytic agents [e.g., alteplase]). Patients receiving such combination therapy should be monitored for bleeding.

[1]. Pentosan polysulfate: a novel therapy for the mucopolysaccharidoses. PLoS One. 2013;8(1):e54459.

[2]. Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro. Antiviral Res. 1988 Sep;9(6):335-43.

[3]. Inhibition of inflammation by pentosan polysulfate impedes the development and progression of severe diabetic nephropathy in aging C57B6 mice. Lab Invest. 2011 Oct;91(10):1459-71.

pentosan sulfate polysaccharide with heparin-like properties.
See also: pentosan sulfate (note moved to); pentosan sodium sulfate (note moved to).

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Drug Indications
Elmiron is indicated for the treatment of adult bladder pain syndrome characterized by glomerular lesions or Henner's lesions, accompanied by moderate to severe pain, urgency, and frequency.

4000-6000

1703.689

140207-93-8

Pentosan Polysulfate;37300-21-3

92043424

White to off-white solid powder

0

50

20

98

3290

0

COC1COC(C(C1OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC2COC(C(C2OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC3COC(C(C3OS(=O)(=O)[O-])OC4C(C(C(C(O4)C(=O)[O-])OC)OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC5COC(C(C5OS(=O)(=O)[O-])OS(=O)(=O)[O-])OC.[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]

MSJQCBORNZDNDU-UHFFFAOYSA-D

InChI=1S/C29H48O50S9.10Na/c1-59-8-4-63-27(21(77-86(50,51)52)12(8)71-80(32,33)34)68-11-7-65-28(22(78-87(53,54)55)15(11)74-83(41,42)43)67-9-6-64-26(66-10-5-62-25(61-3)20(76-85(47,48)49)14(10)73-82(38,39)40)19(13(9)72-81(35,36)37)70-29-23(79-88(56,57)58)17(75-84(44,45)46)16(60-2)18(69-29)24(30)31;;;;;;;;;;/h8-23,25-29H,4-7H2,1-3H3,(H,30,31)(H,32,33,34)(H,35,36,37)(H,38,39,40)(H,41,42,43)(H,44,45,46)(H,47,48,49)(H,50,51,52)(H,53,54,55)(H,56,57,58);;;;;;;;;;/q;10*+1/p-10

decasodium;3-methoxy-6-[2-(6-methoxy-4,5-disulfonatooxyoxan-3-yl)oxy-5-[5-(5-methoxy-3,4-disulfonatooxyoxan-2-yl)oxy-3,4-disulfonatooxyoxan-2-yl]oxy-4-sulfonatooxyoxan-3-yl]oxy-4,5-disulfonatooxyoxane-2-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)