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

• Published in: Drug Metabolism and Pharmacokinetics Vol. 16; no. 6; pp. 553 - 557
• Main Authors: WASHIO, Takuo, EBINE, Hiroki, KOHSAKA, Kazuhiro, TAKAO, Atsushi, NEMOTO, Kazue, YAMASHITA, Kouwa, NOGAMI, Takashi, TSUTSUMI, Shuichiro, KAWASHIRO, Takashi, SHIMIZU, Yayoi
• Format: Journal Article
• Language: English
• Published: The Japanese Society for the Study of Xenobiotics 2001
• Subjects: Absorption; Cevimeline hydrochloride hydrate; Dog; Excretion; Metabolism; SNI-2011
• ISSN: 0916-1139
• DOI: 10.2133/dmpk.16.553

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.