Pharmacokinetics of SNI-2011. (2): Absorption, Excretion and Metabolism of 14C-SNI-2011 in Dogs

Autor: Kazue Nemoto, Shuichiro Tsutsumi, Takashi Kawashiro, Hiroki Ebine, Kouwa Yamashita, Takuo Washio, Kazuhiro Kohsaka, Atsushi Takao, Yayoi Shimizu, Takashi Nogami
Rok vydání: 2001
Předmět:
Zdroj: Drug Metabolism and Pharmacokinetics. 16:553-557
ISSN: 0916-1139
DOI: 10.2133/dmpk.16.553
Popis: 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 Sjogren'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.
Databáze: OpenAIRE