2001 年 16 巻 6 号 p. 553-557
The absorption, excretion and metabolism of SNI-2011, a novel muscarinic acetylcholine receptor agonist developed as an agent improving the symptoms of dry mouth or dry eye caused by Sjögren's syndrome, were studied in dogs.
1. After a single oral administration of 14C-SNI-2011 to male dogs, blood and plasma level of radioactivity reached the maximum at approximately 1 hour, and declined by the bi-exponential manner. Blood and plasma half-lives of radioactivity in α phase were similar, however, blood half-life in β phase was longer than that observed in plasma. The distribution of radioactivity in blood cell was 27-54% up to 8 hours, and then increased with time reaching the values of more than 80% at 24 hours.
2. Cumulative excretion rates of radioactivity in urine and feces were approximately 95% and 0.7%, respectively, within 168 hours after administration, indicating that the main elimination route is the urinary tract.
3. Plasma concentrations of SNI-2011 N-oxide (SNI-NO) were 32 and 23 times higher in male and female dogs, respectively, than those of unchanged form. Main metabolite found in dog's urine was also SNI-NO.
4. There was no sex-related difference in blood and plasma concentration, excretion and metabolism of SNI-2011 in dogs after a single oral administration.