Colestilan

Colestilan is a non-absorbed, non-calcium, non-metallic phosphate-binding polymer. The binding sites become partially protonated in the stomach and interact through ionic and hydrogen bonding with both dietary phosphate anions and bile acids in the duodenum. By binding phosphate from food in the digestive tract, colestilan lowers the serum phosphorus concentration. Colestilan also binds bile acids, thereby lowering the serum LDL-cholesterol concentration. Changes in the bile acid pool in the gastrointestinal tract have also been observed to lower serum glucose. Colestilan may also bind uric acid in the gastrointestinal tract.

Colestilan is not absorbed from the gastrointestinal tract of healthy volunteers following oral administration of ¹⁴C-radiolabelled colestilan.

The results of in vitro testing suggest that medicinal products with anionic and/or lipophilic characteristics have a higher potential to bind to colestilan.

Non-clinical data reveal no direct special hazard for humans based on conventional studies of safety pharmacology, single- and repeated-dose toxicity, genotoxicity, carcinogenic potential or toxicity to reproduction and development. However, reproductive toxicity studies were not conducted at doses higher than 2.5 times the human clinical dose, and the possible reproductive effects related to coagulation and bleeding have not been assessed.

Haemorrhage and increased clotting parameters (PT and aPTT) were evident in rats following repeat administration. These were considered to result from a deficiency of vitamin K following a reduction in the absorption of fat-soluble vitamins.