Pharmacokinetics and safety of T-593 (Osutidine), a new anti-ulcer agent, in healthy volunteers at phase I study

The pharmacokinetics and safety of T-593 (Osutidine), a new anti-ulcer agent, were investigated in healthy male volunteers at doses of 100, 200, 400 and 800 mg in single-dose studies, and at doses of 200 and 400 mg twice daily for 7 days in multiple-dose studies. A study of the effect of food on the pharmacokinetics was also performed by administering a single dose of 200 mg 30 minutes after a meal. A negative T wave was observed on ECGs (12-leads) in one subject treated with multiple doses of 400 mg. However, this event might not be a clinically relevant change judging from the fiat T wave observed prior to drug administration in this subject. In the laboratory data, transient increases in GPT were observed in some subjects, but these changes were slight and not clinically relevant. Mean plasma concentrations of T-593 peaked 2.2-4.2 hours after single administration of 100, 200, 400, and 800 mg, and thereafter were eliminated with half-lives of 2.85-4.59 hours. The increase in C(max) and the area under the curve (AUC) for the plasma concentration versus time of T-593 were proportional to the doses employed. In all the dose groups, 2.38-3.04% of the given dose was excreted unchanged in the 24-hour urine. Food ingestion decreased C(max) and AUC by approximately 1/2 and 2/3, respectively, and prolonged the half-life of elimination to 7.08 hours from 4.37 hours in the corresponding fasting subjects. In the multiple-dose study, the pharmacokinetic parameters of T-593 on days 1, 4 and 7 were almost the same. No accumulation of T-593 was observed during the multiple-dose studies. T-593M1, T-593M2 and T-593M3 were detected in plasma and urine. The half-lives of elimination and the T(max) of these metabolites were the same as that of T-593, indicating that the metabolism of T-593 in humans may not differ from that of rodents and dogs.