Pharmacokinetics of a New Benzimidazole Sulfoxide Derivative, E3810 (1): Pharmacokinetics in Rats and Dogs

Abstract

The pharmacokinetics of E3810 was investigated in rats and dogs. E3810 and its metabolites in plasma were measured by HPLC.
After a single intraduodenal administration of E3810 (5, 20 and 80 mg/kg) to male rats, the drug was absorbed rapidly and showed t_max at 5 minutes. The elimination half life of E3810 in plasma ranged from 6 to 8 minutes. The relation ship between dose and AUC was not linear, and the mean bioavailability was 36.6% after administration of 20 mg/kg. Following a single intraduodenal administration (20 mg/kg) to female rats, the mean bioavailability was 90.7% and higher than that of males.
When male and female rats were orally given 2-20 mg/kg of E3810, the bioavailabilities were 4.1-21.1% without sex difference. The AUCs after oral doses in males and females were smaller than those after intraduodenal doses, because of unstability of E3810 under acidic conditions such as those present in the gastric juice.
After a single oral administration of doses of 0.5, 1.5 and 5 mg/kg to the fasted dogs, being given oral dosing of 1% sodium bicarbonate solution before and after the administration of E3810, the plasma levels reached a peak at 8-12 minutes after dosing. The elimination half lives were 21-26 minutes. The relationship between dose and AUC was approximately linear and the bioavailability at a dose of 1.5 mg/kg was 81.4%. When the secretion of gastric juice was stimulated by pentagastrin given intramusculory, the plasma level of E3810 was markedly lower than that in untreated dogs.