Vol.56 No.S-1 April 2008
Open study of sitafloxacin in patients with respiratory tract infections -PK/PD study-
1)Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, 986-2 Keya, Tarami, Isahaya, Nagasaki, Japan
2)Keio University School of Medicine
3)Research Division for Department of Anti-Infective Agents, Institute of Development, Aging and Cancer, Tohoku University
4)Department of Internal Medicine, Shinrakuen Hospital
5)Department of Clinical Infectious Diseases, School of Medicine, Showa University
6)Division of Molecular and Clinical Microbiology, Department of Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences
7)Field of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
8)Department of Pharmacology, Jikei University School of Medicine
9)Department of Infectious Diseases, Tokyo Women's Medical University
Abstract
Sitafloxacin(STFX), a fluoroquinolone antimicrobial agent, has a broad spectrum of activity and a potent antimicrobial activity against Streptococcus pneumoniae which is a major pathogen in respiratory tract infections(RTI). This clinical study was conducted to confirm the clinical recommended dose of STFX as 50 mg b.i.d. for RTI from PK/PD.
Clinical efficacy was 92.3% (96/104) in the 50 mg b.i.d. group and 93.1% (27/29) in the 100 mg b.i.d. group. Bacteriological efficacy was 89.1% (57/64) in the 50 mg b.i.d. group and 82.4% (14/17) in the 100 mg b.i.d. group. Eradication of major causative organisms was 91.7% (22/24) in S. pneumoniae and 100% (24/24) in Haemophilus influenzae.
Steady state Cmax and AUC0-24h after repeated oral administration of STFX to patients with RTI were 0.57±0.21 μg/mL and 9.38±4.24 μg·h/mL in the 50 mg b.i.d. group, and 1.17±0.45 μg/mL and 17.16±6.52 μg·h/mL in the 100 mg b.i.d. group.
If Cmax/MIC was 5 or below, or AUC0-24h/MIC was 100 or below, eradication were 33.3% (3/9) or 40.0% (4/10). In contrast, if Cmax/MIC was over 5, it was 96.3% (79/82). If AUC0-24h/MIC was over 100, it was 96.3% (78/81). MIC90 of STFX against the causative organisms in this study was 0.1 μg/mL. Results suggest that 50 mg b.i.d. of STFX can achieve Cmax/MIC 5 and AUC0-24h/MIC 100 against 90% of the causative organisms in RTI.
Adverse drug reactions(ADR) occurred in 43.5% (50/115 patients) in the 50 mg b.i.d. group and 42.4% (14/33 patients) in the 100 mg b.i.d. group. The major ADR was diarrhoea (20/148, 13.5%). Cmax and AUC0-24h of patients in whom diarrhoea or soft stool occurred tended to be higher than in patients free of these symptoms. No severe ADRs were observed in either groups.
Results suggest that a dose of 50 mg b.i.d. of STFX is optimal in the treatment of RTI.
Key word
respiratory tract infection, PK/PD, sitafloxacin, fluoroquinolone
Received
December 28, 2007
Accepted
February 8, 2008
Jpn. J. Chemother. 56 (S-1): 63-80, 2008
