Studies on the Metabolic Fate of (±)-2-(Dimethylamino)-1-[[o-(m-methoxyphenethyl)-phenoxy]methyl]ethyl hydrogen succinate hydrochloride (MCI-9042) (IV): Absorption, Metabolism and Excretion after a Single Administration to Dogs

Abstract

The absorption, metabolism and excretion of MCI-9042 were investigated in male and female dogs after oral (20mg/kg) or intravenous (1 mg/kg) administration of ¹⁴C-MCI-9042.
1. After oral administration of ¹⁴C-MCI-9042 to male and female dogs, both the plasma levels of radioactivity and unchanged MCI-9042 reached maxima at 15 ?? 45 min, and then decreased with half-lives (t_1/2β) of 10.3 ?? 10.7hr and 1.5 ?? 1.6hr when determined based on radioactivity or unchanged MCI-9042, respectively. The absorption rate and bioavailability calculated from areas under the time versus plasma concentration curves (AUC₀^∞) of radioac tivity and unchanged MCI-9042 after oral or intravenous administration were 84% and 57%, respectively.
2. After oral administration to dogs, M-1, M-6 and M-8 were detected in the plasma, and other free metabolites were not observed.
3. In both male and female dogs, approximately 100% of dosed radioactivity was excreted into urine(26 ?? 31%) and feces (71 ?? 74%) within 120hr after oral and intravenous administration of ¹⁴C-MCI-9042.
4. Both blood or plasma levels and excretion rates were not affected by sex-related phenomena in dogs.