Open study of sitafloxacin in patients with respiratory tract infections - PK/PD study

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 C_max and AUC_0-24h after repeated oral administration of STFX to patients with RTI were 0.57 ± 0.21 μg/mL and 9.38 ± 424 μg · h/mL in the 50 mg b.i.d, group, and 1.17 ± 0.45 μg/mL and 17.16 ± 6.52 χ • h/mL in the 100 mg b.i.d. group. If C_max/MIC was 5 or below, or AUC_0-24h/MIC was 100 or below, eradication were 33.3% (3/9) or 40.0% (4/10). In contrast, if C_max/MIC was over 5, it was 96.3% (79/82). If AUC_0-24h/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 C_max/MIC5 and AUC_0-24h/ 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%). C_max and AUC_0-24h 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.