Vol.59 No.S-1 May 2011

Phase I study of intravenous levofloxacin in healthy adult male volunteers

Kohya Shiba¹⁾ and Hiroyuki Fukase²⁾

¹⁾Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, Japan
²⁾CPC Clinic, Medipolis Medical Research Institute

Abstract

We evaluated the pharmacokinetics and safety of intravenous levofloxacin(LVFX), a quinolone antimicrobial agent, administered intravenously as single or multiple doses once daily for 7 days in healthy Japanese adult male volunteers. Single dose LVFX infusion time was 250 mg(60 minutes), 500 mg(60 minutes), 750 mg(60 or 90 minutes), or 1,000 mg(120 minutes) and multiple dose 500 mg(60 minutes) or 750 mg(90 minutes).
Following a single intravenous dose of LVFX 500 mg, C_max was 9.79 μg/mL, AUC_0-inf 52.09 μg·h/mL, and t_1/2 8.05 hours. C_max increased dose-proportionally and AUC_0-72h extra-dose-proportionally, with single LVFX doses over a range of 250-750 mg in 60-minute infusion. Cumulative LVFX urinary excretion at 72 hours was similar regardless of dose, in a range of 83.5-96.7%. LVFX was excreted largely unchanged in urine. On day 7 after once-daily multiple intravenous doses of LVFX 500 mg, C_max was 9.97 μg/mL, AUC_0-24h 54.11 μg·h/mL, and t_1/2 9.03 hours. With repeated dosing, the plasma LVFX concentration immediately before dosing remained essentially unchanged on days 2-7, with no drug accumulation seen.
No clinically significant adverse events were reported. Intravenous LVFX was well tolerated at doses up to 1,000 mg when administered as a single dose and up to 750 mg when administered as once-daily multiple doses for 7 days.

Key word

levofloxacin, injection, phase I study, pharmacokinetics

Received

November 10, 2010

Accepted

February 23, 2011

Jpn. J. Chemother. 59 (S-1): 1-9, 2011