Orally absorbed pentosan polysulfate sodium undergoes partial desulfation in the liver and spleen and partial depolymerization in the kidneys to form a large number of metabolites. Desulfation and depolymerization pathways can become saturated with continued dosing.
The fraction of pentosan polysulfate sodium that is absorbed is metabolized by partial desulfation in the liver and spleen, and by partial depolymerization in the kidney to a large number of metabolites. Both the desulfation and depolymerization can be saturated with continued dosing.
IDENTIFICATION AND USE: Elmiron (Pentosan polysulfate) 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 associated with interstitial cystitis. It is also used in veterinary medicine. HUMAN STUDIES: Elmiron, a highly sulfated, semisynthetic pentose polysaccharide with properties similar to heparin, is used for the treatment of interstitial cystitis. Overdose of Elmiron has not been reported. Based upon the pharmacodynamics of the drug, toxicity is likely to be reflected as anticoagulation, bleeding, thrombocytopenia, liver function abnormalities, and gastric distress. A case of severe thrombocytopenia and ischemic stroke following Elmiron treatment has been reported. The development of thrombocytopenia was reported in 25 patients receiving either heparin or Elmiron over a 7 month period. Based on platelet aggregation studies it was suggested that an immune allergic reaction to the anticoagulants occurred. ANIMAL STUDIES: Elmiron was orally administered once daily via gavage, 5 days per week, for up to 2 years. The dosages administered to mice were 56, 168 or 504 mg/kg. The dosages administered to rats were 14, 42, or 126 mg/kg for males, and 28, 84, or 252 mg/kg for females. Elmiron was carcinogenic to mice but not rats. Increased incidences of liver hemangiosarcoma, hepatocellular neoplasms (predominantly adenomas), and malignant lymphomas revealed carcinogenic activity of Elmiron in female mice. Reproduction studies have been performed in mice and rats with intravenous daily doses of 15 mg/kg, and in rabbits with 7.5 mg/kg. These studies did not reveal evidence of impaired fertility or harm to the fetus from Elmiron. Elmiron sodium was not clastogenic or mutagenic when tested in the mouse micronucleus test or the Ames test (Salmonella typhimurium).
Evaluation: There is inadequate evidence in humans for the carcinogenicity of pentosan polysulfate sodium. There is sufficient evidence in experimental animals for the carcinogenicity of pentosan polysulfate sodium. Overall evaluation: Pentosan polysulfate sodium is possibly carcinogenic to humans (Group 2B).
Sprague-Dawley rats were given (3)H-labelled pentosan orally or intravenously at a dose of 5 mg/kg bw, and killed 1 or 4 hours later, respectively. Autoradiography indicated extensive distribution of radiolabel in the whole animal after intravenous administration, with notable labelling of connective tissues, and low activity in bone and cartilage. There was a high concentration of radiolabel in the urine, and preferential localization of radiolabel to the lining of the urinary tract. After oral administration, the tissue distribution of radiolabel was similar, but activity was lower.
In rabbits given 1.0-1.2 mg pentosan by oral administration, median recovery in the urine was 7.45% (range, 2.1-46.0%) for pentosan of low relative molecular mass, and 0.1% (range, 0.0-0.3%) for pentosan of high relative molecular mass.
In rabbits given 1-1.2 mg of pentosan by intravenous administration, median recovery in the urine was 47.2% (range, 19.7-73.2%) for unfractionated pentosan, 74.6% (range, 31.4-96.3%) for pentosan of low relative molecular mass, and 3.3% (range, 2.5-5.0%) for pentosan of high relative molecular mass.
Excretion of pentosan was studied in 34 female patients with interstitial cystitis who were receiving long-term treatment with pentosan. The median concentration of pentosan in the urine of these patients was 1.2 ug/mL (range, 0.5-27.7 ug/mL). All the pentosan recovered from the urine of these patients was of low relative molecular mass.
来源:Hazardous Substances Data Bank (HSDB)
制备方法与用途
生物活性
Pentosan Polysulfate Sodium 是一种口服生物可利用的半合成药物，具有抗炎和促软骨生成的特性。此外，它也是一种有效且选择性的抗 HIV 药物，并用于间质性膀胱炎的研究。
