SAFETY, TOLERABILITY AND PHARMACOKINETICS OF THE NEW LONG-ACTING QUINOLONE DW-116 AFTER SINGLE AND MULTIPLE DOSING IN HEALTHY-SUBJECTS

Citation
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
Citations number
15
Categorie Soggetti
Microbiology,"Pharmacology & Pharmacy","Infectious Diseases
Journal title
Journal of antimicrobial chemotherapy
ISSN journal
03057453 → ACNP
Volume
42
Issue
3
Year of publication
1998
Pages
349 - 361
Database
ISI
SICI code
Abstract
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.