Grepafloxacinの臨床第一相試験

DOI 被引用文献5件 参考文献9件

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  • Phase I study of grepafloxacin

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A Phase I study of grepafloxacin (GPFX), a new synthetic antibacterial agent, was conducted to determine the safety and pharmacokinetics of the compound in healthy adult male volunteers.<BR>GPFX was administered orally to fasted volunteers in single doses of 10, 25, 50, 100, 200, 300 and 400mg and in 7-day multiple doses of 200 mg twice daily and 300 mg once daily. The effect of a meal was also investigated at 200 mg.<BR>In 47 healthy adult male volunteers, the subjective and objective symptoms observed were headache in 3 volunteers, dull headache in 1 volunteer, light-headed feeling in 1 volunteer and bitter tasete in 1 volunteer. Abnormal laboratory test values were slightly increased BUN and GPT in one volunteer each. However, all of these symptoms and changes were mild and transient. No GPFX-related abnormalities were observed in any other parameters.<BR>The plasma concentrations of GPFX increased dose-dependently after single oral administration, indicating maxima of 0.41, 0.66, 0.99 and 1.62 μg/ml at 100, 200, 300 and 400 mg, respectively, in fasting volunteers. The elimination half-life (T1/2) of the plasma concentration in the β phase was 11.0- 12.5 hours. The cumulative urinary excretion during the the first 0-72 hours was 10.0%-12.6%. The fecal excretion of unchanged GPFX during the period of 0-72 hours was 31.5% of the administered dose. The meal had no effect on the absorption of GPFX by the digestive tracts. The change in the saliva concentration after single administration at 200 mg was similar to that in the plasma concentration, and the transfer ratio (ratio of the plasma concentration to the saliva concentration) at 1.5-4 hours was about 0.4-0.6. The plasma concentration in repeated administration at 200 mg twice daily and 300 mg once daily for 7 days reached a steady-state on the fourth day of multiple dosing, and no accumulation was found. These results suggested that, from the safety point of view, it is possible to perform further clinical evaluation.

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