Absorption, distribution, metabolism and excretion of [carbonyl-14C]mosapride citrate after repeated oral administration in rats.

Absorption, distribution, metabolism and excretion of mosapride citrate ((+/-)-4-amino-5-chloro-2-ethoxy-N [[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate, AS-4370, CAS 112885-42-4), a novel gastrokinetic agent, were studied with 14C-labeled compound in male rats during and after 21 consecutive daily oral administration at a dose of 10 mg/kg/d. After the first administration, plasma radioactivity concentrations were essentially equal to those in the single dose experiment, including the maximum concentration (Cmax; 1130 ng eq./ml) at 1 h. Plasma concentrations at 1 h after each administration were virtually constant in the range of 770-1350 ng eq./ml for 21 days. On the other hand, the plasma concentration at 24 h gradually increased for 6-7 days to about 120 ng eq./ml and became substantially constant, suggesting that apparent steady state was achieved by around 7 consecutive daily administration. Plasma concentration reached Cmax of 1230 ng eq./ml at 0.5 h after the 21st administration and decreased biphasically with half-lives of 3.4 h (t1/2 alpha) and 14.9 h (t1/2 beta). t1/2 alpha was virtually similar but t1/2 beta was about 2 times longer compared with single dose experiment. About 40% and 55% of dose radioactivity were excreted in urine and feces, respectively, for 21 days and radioactivity was almost completely excreted within 168 h after the last administration. The analysis by thin layer chromatography elucidated that composition of radioactive metabolites in plasma and urine after repeated administration was similar to that in the single dose study.(ABSTRACT TRUNCATED AT 250 WORDS)