Pharmacokinetics and urinary excretion of DW116, a new fluoroquinolone antibacterial agent, in humans as a phase I study

Abstract

Pharmacokinetics and urinary excretion of the new fluoroquinolone antibacterial agent DW116 [1-(5-fluoro-2-pyridyl)-6-fluoro-7-(4-methyl-1-piperazynyl)-1,4-dihydro-4-oxoquinolone-3-carboxylic acid, hydrochloride] following oral administration (200, 400, 600 mg) were studied in humans as a phase I study. The plasma concentration of DW116 declined monoexponentially with a half-life range of 16-22 hr. The area under the curve (AUC) and C-max increased proportionally as the dose increased. The T-1/2 and mean residence time (MRT) (28.3-30.9 hr) were independent of dose. The T-max appeared within 3 hr (0.9-2.7 hr) after drug administration. The K-a ranged from 1.3 to 4.1 (hr(-1)). The plasma half-life was much longer, and C-max was higher by about two- to three-fold than conventional fluoroquinolones. Urinary recovery of DW116 was 29.6-61.6% of the dose. The maximum excretion rate appeared within 4 hr and decreased continuously after drug administration. A urinary metabolite was not detected in the urine extract obtained before and after hydrolysis by beta-glucuronidase (from Escherichia coli); this was different from other fluoroquinolone antibacterial agents. Poor metabolism in the kidney may contribute to the good oral bioavailability, but due to the low recovery (< 60%) in urine, it is possible that DW116 is metabolized in the liver or other organs.