Absorption and excretion of colestilan in healthy subjects

Colestilan, an anion-exchange resin binding both phosphate and bile-acid anions, is under development for the treatment of hyperphosphataemia and dyslipidaemia, which occur in the majority of end-stage renal disease patients. This study using 14C-colestilan was conducted to investigate the absorption and excretion of colestilan in humans. Following a 28-day run-in period with administration of colestilan 3 g three times daily, 12 subjects received a single oral dose of 14C-colestilan 100 mg (approximately 4.0 MBq) and colestilan 3 g under fasted conditions on the morning of day 1. A total of 9 g of colestilan was administered three times daily on days 1-4. Total radioactivity levels in whole blood (at 4, 8, 12 and 24 hours and then at 24-hour intervals) and in the urine and faeces (from 0 to 24 hours and then at 24-hour intervals) were monitored up to 216 hours postdose (day 10). Total radioactivity measured in all whole-blood samples was below the lower limit of quantification (0.025 microg equivalent of 14C-labelled colestilan/mL of whole blood). Total radioactivity assessed in all urine samples was also below the lower limit of quantification (0.003 microg equivalent/mL for urine), except at 0-24 hours postdose, when 0.01% of the radioactive dose was excreted by all subjects. This level was below the predetermined water soluble impurity level of 0.04%. The mean cumulative excretion of total radioactivity in the faeces was 99.66% by 216 hours postdose, excluding one subject with incomplete collection of faecal samples. These results demonstrate that colestilan is not absorbed from the gastrointestinal tract and is completely excreted in the faeces.