Sucralfate: pharmacokinetics, metabolism and selective binding to experimental gastric and duodenal ulcers in animals

Pharmacokinetics, metabolism, and binding capability of a basic aluminium salt of sucrose octasulphate (sucralfate, Ulcogant) to ulcer lesions were investigated in Wistar rat, Beagle dog, Rhesus, and Cynomolgus monkey with 14C-labelled material. After i.v. injection in rats the 14C-radioactivity has a very short serum half-life of 1 h and is excreted almost completely by the kidneys. After oral administration only a very small portion of the dose is detectable in serum which is eliminated rapidly from the intravascular space. From the renal excretion data it is concluded that sucralfate is absorbed from the gastrointestinal tract of rat, Beagle dog, and Rhesus monkey only from 1% to 5% of the dose. The radioactive constituents in plasma, urine, and feces of rat and Cynomolgus monkey were analysed by HPLC. Both after i.v. and p.o. administration only unchanged substance could be detected. A possible binding of 14C-sucralfate to the ulcerated mucosa of stomach and duodenum was investigated in rats by histoautoradiography. The ulcers were induced by acetic acid. A selective accumulation of 14C-sucralfate in the area of the stomach ulcer could be demonstrated as long as 8 h after single p.o. administration. In the duodenum the autoradiographs showed a specific binding of 14C-sucralfate to the ulcerated mucosa at 1, 2, and 4 h after administration. Neither pretreatment with an H2-receptor antagonist nor simultaneous administration of an antacid influenced the binding of 14C-sucralfate. These results suggest that the mode of action of sucralfate is the formation of a protective layer which stops harmful agents like gastric juice and bile from further damaging the ulcerous lesions, thus ensuring an uninterrupted healing process. The very small extent of absorption and the rapid excretion from the organism minimize the risk of a systemic burden.