Abstract
A phase I study of brotizolam has been performed with 9 healthy male Japanese volunteers. After a single oral administration of 0.125 mg, 0.25 mg and 0.5 mg in 3 volunteers respectively, psychic and physical symptoms, vital signs, ECG, laboratory values (urine, blood and blood chemistry tests) and blood levels were examined.
1. Induction of sleep due to the action of the drug and decrease in blood pressure due to the induced sleep were observed dose-dependently. A tendency of decrease in respiratory rate was also noted, but it was not a clinically meaningful change. A peak of these effects appeared around 2 hrs after administration and thereafter disappeared gradually in approximate conformity with the change of plasma concentration of brotizolam.
2 . The secondary effects such as unsteadiness, dizziness and dullness, and other symptoms, e. g. dry mouth, were observed, but these symptoms were mild and appearedto have no clinical significance.
3. No abnormal laboratory findings were noted.
4 . Plasma concentration of brotizolam reached its maximum at 0.5-4 hours after oral administration. Almost linear correlation was found in the relations between Cmax and administration doses, and between AUC and administration doses.
The above results establish the safety of brotizolam in healthy Japanese volunteers.
