1997 Volume 12 Issue 4 Pages 275-280
The pharmacokinetics and pharmacological effect of ethyl 2-[4, 5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate (KBT-3022), were studied after administration of KBT-3022 to guinea pigs.
1. The unchanged KBT-3022 was detected in plasma at only early phase after intravenous or oral administration of KBT-3022. KBT-3022 was readily metabolized to desethyl KBT-3022, 2-[4, 5-bis(4-methoxyphenyl)thiazol-2-yl]-pyrrol-1-ylacetic acid.
2. Both Cmax and AUC00-∞ of desethyl KBT-3022 increased approximately in proportion to the administerd dose over the dose range 5-20 mg/kg.
3. The levels of radioactivity in the pla telets were 9-44 times higher than those in plasma after oral administration of 14C-KBT-3022, and the level of desethyl KBT-3022 in the platelets was estimated to be about 75 times higher than that in plasma.
4. TXB2 production was almost completely inhibited by 48h after oral administration of KBT-3022 both at a dose of 1 and 5 mg/kg, but duration of this inhibitory effect at a dose of 5 mg/kg was longer than that at a dose of 1 mg/kg. IC50 value of desethyl KBT-3022 in plasma was estimated to be 1-2 ng/ml.
