Metabolism of [3H]pentosan polysulfate sodium (PPS) in healthy human volunteers

Pentosan polysulfate sodium (PPS) is the active ingredient in ELMIRON (R), a drug approved for the relief of bladder pain associated with interstitial cystitis. The study objective was to characterize the pharmacokinetic and metabolic profiles of PPS following oral dosing of [H-3]PPS. As specific assays for PPS do not exist, metabolic profiling was accomplished through multiple fraction collections and radiochromatographic techniques. Two groups of eight healthy female subjects sequentially received a single oral dose of 200 mu Ci [H-3]PPS supplemented with 300 mg unlabelled PPS or 300 mu Ci [H-3]PPS supplemented with 450 mg unlabelled PPS. Most of the administered dose (84%) was excreted in facces as intact PPS, and a smaller percentage (6%) was excreted in urine. In summary, orally administered PPS was very poorly absorbed, with the majority of the drug being excreted in faeces as intact PPS and in urine as low molecular weight and desulfated PPS.