Pentosan polysulfate sodium
Pentosan polysulfate sodium. Semi-synthetic glycosaminoglycan mimetic, made by chemically sulfonating a plant-derived beta-(1,4)-xylan. Orally it is the only drug…
Semi-synthetic glycosaminoglycan mimetic, made by chemically sulfonating a plant-derived beta-(1,4)-xylan. Orally it is the only drug approved for interstitial cystitis, where the proposed action is local: replenishing a defective glycosaminoglycan layer on the bladder urothelium so that urinary solutes stop reaching the underlying tissue. Parenterally it behaves as a heparin-like polyanion, raising APTT and anti-Xa activity and releasing lipases, and in that form it has been used for osteoarthritis and studied in Kaposi sarcoma. Long-term oral use is now associated with a distinctive pigmentary maculopathy, which is the dominant safety consideration.
NO mw_g_mol ON PURPOSE. PubChem CID 92043424 gives 1705.1 for a single defined decasodium oligomer, which is not the drug; the drug is a distribution, "4000 to 6000 Da" verbatim (PMID:31287456). Storing either number would misdescribe it, and a µM conversion on a polydisperse polyanion is meaningless anyway. REJECTED MW: PMID:32088260 contains "average molecular weight (MW) up to 4000-8000 Dalton" and that sentence is about HEPARIN, not PPS. THE ASSAY GOVERNS EVERYTHING HERE, which is why this is a mixture rather than a gap. Faaij 1999 (PMID:10192753), 18 healthy young men, three-way crossover of 1500 mg PO against 50 mg IV: "Point estimates for the oral bioavailability of PPS were in the range of 0% with small confidence intervals" and "The oral bioavailability of PPS is negligible in young healthy males" — measured through APTT, anti-Xa, hepatic triglyceride lipase, lipoprotein lipase, t-PA and fibrin plate lysis, because no specific assay exists. Simon 2005 (PMID:16278190), 16 healthy women given [3H]PPS orally: "Most of the administered dose (84%) was excreted in faeces as intact PPS, and a smaller percentage (6%) was excreted in urine", the urinary material being "low molecular weight and desulfated PPS" — a metabolite, not the drug. That near-zero oral bioavailability is the single most decision-relevant fact about the oral product and it has no field to live in: F must be a fraction the solver multiplies a dose by, and this record has no curve to multiply. AN F OF 0 WOULD BE THE WRONG SHAPE, not a smaller number. The IV data are detectability, not kinetics: "PPS was still detectable 8 h after 50 and 100 mg IV and 6 h after 35 mg SC" (PMID:2436330, three subjects, one per level), measured by covalent complex formation with heparin cofactor II on SDS-PAGE. TWO MORE TRAPS: PMID:2433788's only Tmax-like figure ("maximal plasma concentrations reached 2-3 h after injection") is UNFRACTIONATED HEPARIN's, not SP54's; and PMID:1690285's rabbit "approximately 1 h 24 min" is stated jointly for "dextran sulfate and pentosan polysulfate ... these compounds", so it is not PPS-specific. PMID:1726041 is titled as the IV human PK study and HAS NO ABSTRACT IN PUBMED — full text is the unlock, and it is in AUTHORING_GAPS. Doses: oral 300/600/900 mg daily in the interstitial-cystitis RCT (PMID:11378052, 376 analysed) with the marketed regimen 100 mg three times daily; IV MTD 3 mg/kg/day in Kaposi sarcoma (PMID:7692072); IM and SC regimens from PMID:2422778. Mechanism reference PMID:9679938 (rabbit bladder permeability barrier).
Sources: PMID:10192753, PMID:16278190, PMID:31287456, PMID:2436330, PMID:11378052, PMID:9679938