Vol.57 No.S-2 July 2009

Levofloxacin 500 mg pharmacokinetics in patients with impaired renal function

Kazushige Hanaoka¹⁾, Kazuya Kawahara²⁾, Satoru Nagashima³⁾ and Seiji Hori⁴⁾

¹⁾Division of Kidney and Hypertension, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan
²⁾Kawahara Nephro-Urological Clinic
³⁾Shitoro Clinic
⁴⁾Department of Pharmacology, Jikei University School of Medicine

Abstract

To explore safer dosage for patients with infectious disease, we studied the impact of renal function on levofloxacin(LVFX) pharmacokinetics in patients with varying degrees of impaired renal function. Patients were orally administered LVFX 500 mg and plasma concentrations were measured. Appropriate dosage adjustment was determined by simulating LVFX plasma concentration based on pharmacokinetic parameters in patients with various degrees of renal impairement.
Patients were classified into three groups based on C_cr, i.e., C_cr≥50 mL/min (Group I), 20 mL/min≤C_cr<50 mL/min (Group II), and C_cr<20 mL/min (Group III).
After single oral administration of LVFX 500 mg, plasma AUC_0-72h for Group I patients was 81.7 μg·h/mL, for Group II patients 151.0 μg·h/mL, for Group III patients 250.7 μg·h/mL. t_1/2 was 9.2 h for Group I patients, 15.9 h for Group II patients, and 33.7 h for Group III patients. These results indicate that AUC_0-72h increased and t_1/2 was prolonged as renal function became increasingly impaired.
LVFX urinary excretion within 48 hours after the dose decreased with renal impairment severity. Mean urinary excretion (dose %) was 80.0% for Group I patients, 56.4% for Group II patients, and 28.3% for Group III patients.
We simulated plasma concentration during 7-day LVFX 500 mg treatment once daily using pharmacokinetic parameters for patients in each group, finding that exposure to LVFX in Group I patients did not change during treatment. LVFX exposure in Groups II and III patients, however, increased over the treatment period (Days 1 to 7).
An examination of possible dosage adjustment in plasma concentration simulation after repeated LVFX administrations, suggested the following: a suitable dosage for Group II patients is an initial dose of 500 mg followed by 250 mg once daily, and that for Group III patients would be an initial dose of 500 mg followed by 250 mg every second day.
In conclusion, our results provide a rationale for appropriate LVFX dosage and dosing intervals for patients with renal impairment.

Key word

levofloxacin, renal dysfunction, pharmacokinetics, single administration

Received

December 18, 2008

Accepted

May 21, 2009

Jpn. J. Chemother. 57 (S-2): 12-19, 2009