Absorption, Distribution and Excretion of SM-10888 in Rats

9-Amino-8-fluoro-1, 2, 3, 4-tetrahydro-2, 4-methanoacridine citrate (SM-10888) was given to rats orally or intravenously, and its absorption, distribution and excretion were investigated. 1. After a single oral administration of 14C-SM-10888 (5mg/kg), the serum 14C level reached a maximum at 30min (1.09μg eq./g), with an AUC value corresponding to about 90% of that observed after intravenous administration, clearly revealing rapid and efficient absorption from the gastrointestinal tract. Under fasted conditions, Cmax was 2-fold higher than that of non-fasted animals, without significant change in AUC, suggesting that diet causes delayed absorption. Both Cmax and AUC increased as the dose was raised from 1 to 20mg/kg. Repeated dosing (5mg/kg/day for 14 days) exerted little effect on serum 14C levels. 2. After a single oral administration of 14C-SM-10888 (5mg/kg), the radioactivity was distributed throughout the body, with relatively higher activities being observed in the digestive tract, the liver and the salivary gland. Radioactivity in each tissue had drastically decreased by 24hr post administration. 3. After a single oral administration of 14C-SM-10888 (5mg/kg), cumulative excretion into the urine and feces after 168hr was 52.2% and 44.2%, respectively. When administered to bile-duct cannulated rats, cumulative excretion after 72hr into the bile and urine was 65.1% and 29.1%, respectively, providing further support for a high absorption rate. Repeated dosing had little effect on the patterns of excretion into the urine and feces.