C. Meyerhoff et al., SAFETY, TOLERABILITY AND PHARMACOKINETICS OF THE NEW LONG-ACTING QUINOLONE DW-116 AFTER SINGLE AND MULTIPLE DOSING IN HEALTHY-SUBJECTS, Journal of antimicrobial chemotherapy, 42(3), 1998, pp. 349-361
The safety, tolerability and pharmacokinetics of DW-116, a new fluoroq
uinolone with a broad antibacterial spectrum, were evaluated in health
y male subjects after administration of single oral doses of 100, 200,
300 and 800 mg and after administration of multiple oral doses of 300
or 400 mg, respectively, for 7 days. DW-116 was well tolerated. Gastr
ointestinal symptoms and skin reactions were noted and considered to b
e possibly related to DW-116. The geometric means of the maximum plasm
a concentrations (C-max) linearly increased with the dose administered
from 1.19 mg/L to 8.73 mg/L after single dose administration. At stea
dy state, the geometric mean minimum and maximum plasma concentrations
were 2.14 and 5.65 mg/L, respectively, after the multiple 300 mg dose
and 2.73 and 8.00 mg/L, respectively, for the multiple 400 mg dose. T
-max varied between 1 and 5 h. The terminal half-life ranged from 11.3
7 to 24.89 h. The geometric mean renal clearance was approximately 30
mL/min. Approximately 45% of the dose was excreted unchanged in urine
within 60 h. There was no clinically relevant deviation from dose prop
ortionality. The changes in steady-state pharmacokinetic parameters wh
en DW-116 was taken before a high-fat breakfast were not clinically re
levant. In conclusion, DW-116 was safe in this study, the first admini
stration to human subjects. Its pharmacokinetics indicate that once-da
ily dosing may be possible.