Vol.57 No.S-2 July 2009

Phase I study of levofloxacin in healthy and elderly volunteers

Kohya Shiba¹⁾, Hiroyuki Fukase²⁾ and Atsushi Sugiyama³⁾

¹⁾Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan
²⁾Medical Corporation Kouryokai CPC Clinic
³⁾Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi

Abstract

To prepare for changing the standard levofloxacin(LVFX) dosage from 100 mg three times a day to 500 mg once daily (qd), we evaluated the LVFX qd safety and pharmacokinetic profile in a single-dose study in healthy Japanese male volunteers given an oral dose ranging from 250 mg to 1,000 mg and in a multiple-dose study in healthy nonelderly and elderly Japanese male volunteers given LVFX 500 mg qd for 7 days. To compare pharmacokinetic profiles in different ethnic groups, we also conducted a study in healthy Caucasian male volunteers given an oral dose of 500 mg.
1. Pharmacokinetics: In the single-dose study, LVFX C_max and AUC_0-72h were 7.35 μg/mL and 57.86 μg·h/mL at a dose of 500 mg. While LVFX C_max increased dose-proportionally, AUC increased above dose-proportionally.
In the multiple-dose study, LVFX C_max, C_24h, and AUC_0-24h on day 7 were higher in elderly than nonelderly subjects. C_min was stable from days 2 through 7 with no clear evidence of accumulation in either the nonelderly or elderly.
Average LVFX C_max and AUC_0-72h were higher in Japanese than Caucasian subjects.
2. Safety: No adverse drug reactions were seen after LVFX administration in any study.
In conclusion, LVFX 500 mg qd was well tolerated, and no accumulation was seen in multiple-dose administration.

Key word

levofloxacin, phase I study, healthy volunteer, pharmacokinetics

Received

December 15, 2008

Accepted

June 2, 2009

Jpn. J. Chemother. 57 (S-2): 1-11, 2009