Sevelamer, a Phosphate-Binding Polymer, is a Non-Absorbed Compound

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Abstract
To examine the absorption, distribution and excretion of sevelamer hydrochloride in rats and humans. Twelve male Sprague-Dawley rats were used in the animal study, and twenty human volunteers participated in the clinical trial. In the animal study, six rats received a single oral dose of [3H]sevelamer and six rats were pretreated with unlabelled sevelamer in the diet for 28 days followed by a single dose of [3H] sevelamer on day 29. Total urine and faeces were collected at intervals up to 72 hours post dose, and tissues were obtained at the time of sacrifice. In the clinical trial, subjects received a single oral dose of [14C]sevelamer following 28 days of pretreatment with unlabelled sevelamer. Blood, urine and faeces samples were collected at intervals up to 96 hours. In the rat study, no significant urinary excretion of radioactivity was observed. The average recovery of radioactivity in the faeces was 98% in the single-dose group and greater than 100% in the group pretreated with unlabelled sevelamer for 28 days. A total of less than 0.1% of the dose was found in the tissues. In the human study, no detectable amount of 14C was found in the blood of any subject at any time. The majority of subjects had no detectable amounts of 14C recovered in the urine. In subjects where 14C was recovered in the urine, less than 0.02% was detected, a level equivalent to the free 14C detected in the [14C]sevelamer preparation. On average, greater than 99% of the administered dose was recovered in the faeces of the subjects. These studies demonstrate that sevelamer is a non-absorbed compound.