Absorption, Distribution and Excretion of a New Antiplatelet Drug, Ethyl 2-[4, 5-bis (4-methoxyphenyl) thiazol-2-yl]pyrrol-1-ylacetate, (KBT-3022), after Single Oral Administration in Mice

Abstract

The absorption, distribution and excretion of ethyl 2-[4, 5-bis (4-methoxyphenyl) thiazol-2-yl]pyrrol-1-ylacetate (KBT-3022) were studied after administration of ¹⁴C-KBT-3022 to mice.
Maximum plasma levels (Cax) appeared at 0.5 hr after oral administration of ¹⁴C-KBT-3022 to fasted male mice and ¹⁴C-KBT-3022 was absorbed from small intestine, especially from jejunum. The radioactivity decreased with half-life of 5-6 hr. The C_max and the area under the plasma concentration-time curve (AUC) were higher in unfasted mice than in fasted mice.
The percentages of radioactivity excreted in urine and feces, whithin 96 hr after intravenous or oral administration of ¹⁴C-KBT-3022 to male mice, were below 1% and above 96% of dose, respectively. The percentages of radioactivity excreted in urine and feces after oral administration of ¹⁴C-KBT-3022 were similar both in male and female mice. The ¹⁴C-KBT-3022 probably is excreted mainly in bile. The radioactivities in the intestine and liver were higher than in plasma, however, radioactivities were rapidly eliminated from tissues so that no significant remaining was observed in the tissue. After oral administration of ¹⁴C-KBT-3022 to fasted mice, the radioactivites in the platelet and aorta were 2.4-15.7 times higher and about 0.5 times lower than that in plasma, respectively. The elimination half-life of radioactivity in the platelet was close to that in plasma. This result shows KBT-3022 is reversibly distributed in platelet.