The in oitro and in vivo antibacterial activity of sitafloxacin (STFX), a quinolone, was compared to that of other quinolones: levofloxacin, ciprofloxacin (CPFX), moxifloxacin, and tosufloxacin. STFX showed the most potent antibacterial activity against clinical isolates of both Gram-positive and Gram-negative bacteria, including quinolone-resistant strains, Mycoplasma pneumoniae, and Chlamydiaceae. MIC₉₀ of STFX against streptococcus pneumoniae, a major respiratory tract infection pathogen was 0.06μg/mL, and was 4-to 64-fold more active than those of other quinolones tested. MIC₉₀ of STFX against Escherichia coli, major urinary tract infection pathogen, was 1μg/mL, and was 16-to 32-fold more active than those of other quinolones tested. In systemic infection caused by major pathogens in mice, STFX showed a protective effect reflecting its potent in vitro antibacterial activity. STFX also showed higher in vitro activity against Pseudomonas aeruginosa than that of CPFX. In a model of complicated urinary tract infection caused by P. aeruginosa in the rat, the therapeutic efficacy of STFX was greater than that of CPFX. A study on the inhibitory effect against DNA gyrase and topoisomerase IV purified from S.pneumoniae and E. coli showed that STFX had higher inhibitory activity than other quinolones tested against both wild-and mutant enzymes, which has single or double aminoacid replacement (s) in the quinolone-resistance-determining region (QRDR). The inhibitory activity of STFX against mutant DNA gyrase and topoisomerase IV, which has single amino-acid replacement in QRDR, corresponded roughly to those of other comparable quinolones against wild-type enzymes.
In an in vitro pharmacokinetic model simulating serum concentrations of STFX following 50mg twicedaily and 100mg twice-daily oral administration, STFX was shown to be bactericidal against staphylococcas aureus, S.pneumoniae, E.coli, P. aeruginosa, Haernophilus influenzae, and Moraxella catarrhalis. Even at lower doses, STFX was bactericidal against S. pneumoniae, H. influennzae, and M. catarrhalis, for which MIC of STFX corresponded to MIC₉₀ of clinical isolates. A study focusing on AUC, the malor pharmacokinetic parameter correlated with pharmacodynamics of quinolones, showed that STFX, with simulated human serum AUC in the mouse, was shown to be highly effective in a model of pneumonia due to penicillin-resistant S.pneumoniae.

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The effect of aging on the pharmacokinetic profile of sitafloxacin (STFX) was investigated by comparing 5 elderly (>65 years) and 6 non elderly (=20 to <40 years) male volunteers.
Following a single oral administration of 100mg of STFX, elderly volunteers showed delayed t_max, prolonged t_1/2, decreased renal clearance, and increased AUC_0-24h compared to non elderly volunteers. No notable differences were observed in cumulative urinary excretion (0-48h). No significant adverse drug reactions were observed in either groups.

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We compared pharmacokinetic profiles of sitafloxacin (STFX) in patients with renal dysfunction divided into 3 creatinine clearance (C_cr) based groups: mild dysfunction (Group I), moderate dysfunction (Group II), and severe dysfunction (Group III). The area under the blood concentration-time curve (AUC) was 4.66μg·h/mL in Group I, 8.04μg·h/mL in Group II, and 9.95μg·h/mL in Group III after STFX administration (50mg). These results indicate that AUC increased with renal dysfunction severity. The half-life was 7.5h in Group I, 11.5h in Group II, and 16.3h in Group III, and prolonged depending on renal dysfunction severity. Urinary excretion (0-48h) was 48.9% in Group I, 44.7% in Croup II, and 20.1% in Group III, and decreased depending ooreuol dysfuoctin severity. Tbeiocidencmofodverme reactions wax 25%(3/12).
Our results suggest that the STFX dosage and dosing interval be determined with care in patient with renal dysfunction.

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The effect of antacid (aluminum hydroxide and magnesium oxide), calcium carbonate, and ferrous sulfate on pharmacokinetics of the fluoroquinolone sitafloxacin (STFX) was evaluated in two separate studies. Each study was a three-period crossover in 9 healthy adult male volunteers involving the administrationof 100mg STFX alone as a control treatment. STFX coadministration with aluminum hydroxide decreased the C_max average to 18%, with magnesium oxide to 43%, with calcium carbonate to 63%, and with ferrous sulfate to 33%. STFX coadministration with aluminum hydroxide decreased the AUC_0-24h, average to 25%, with magnesium oxide to 49%, with calcium carbonate to 68%, and with ferrous sulfate to 44%. These results suggest that coadministering STFX with metal-ion reduced the STFX effect.

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The effect of the H₂ receptor antagonist (ranitidine hydrochloride) on pharmacokinetics of the fluoroquinolone sitafloxacin (STFX) was studied in 8 healthy adult male volunteers in a two-period crossover trial. AUC_0-24h increased by 8% and C_max by 4%, suggesting that ranitidine hydrochloride affected STFX pharmacokinetics negligibly, if at all.

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The clinical efficacy and safety of sitafloxacin (STFX), a fluoroquinolone compound, and levofloxacin (LVFX) were objectively compared in the treatment of patients with pneumonia, secondary infection, or acute exacerbation of chronic respiratory tract disease in a double-blind, randomized, group-comparative study. Patients were treated for 7 days with either STFX 50mg orally twice daily (STFX group) or LVFX 100mg three times daily (LVFX group).
The clinical efficacy rate at the end of treatment in 208 evaluable patients was 92.5%(99/107) in the STFXgroup and 92.1%(93/101) in the LVFX group. STFX was found to be not inferior to LVFX. The clinical efficacy rate was 96.4%(53/55) in the STFX group and 94.0%(47/50) in the LVFX group for pneumonia and 88.5%(46/52) in the STFX group and 90.2%(46/51) in the LVFX group for secondary infection or acute exacerbation of chronic respiratory tract disease. Eradication in 97 patients evaluable for bacteriological response was 78.4%(40/51) in the STFX group and 80.4%(37/46) in the LVFX group. Based on bacterium disappearance by causative bacterium, 95.0%(19/20) of Gram-positive bacteria was eradicated in the STFX group and 87.5%(21/24) in the LVFX group. For Gram-negative bacteria, 79.4%(27/34) was eradicated in the STFX group and 81.5%(22/27) in the LVFX group. The incidence of adverse drug reaction was 29.8%(34/114) in the STFX group and 25.9%(30/116) in the LVFX group.
These results suggest that a 50mg oral dose of STFX twice daily for 7 days is clinically useful in the treatment of respiratory tract infection.

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Sitafloxacin (STFX), a fluoroquinolone antimicrobial agent, has potent antimicrobial activity against Streptococcus pneumoniae, the major pathogenic bacteria in respiratory tract infections. The clinical efficacy and safety of STFX and tosufloxacin (TFLX) were compared in the treatment patients with community-acquired pneumonia in a double-blind, randomized, group-comparative study. Patients were treated orally twice daily 7 days with either STFX at 100 mg (STFX group) or TFLX at 150 mg three times daily (TFLX group).
Clinical efficacy in 225 patients was 93.3%(111/119 patients) in the STFX group and 89.6%(95/106 patients) in the TFLX group. STFX was found to be not inferior to TFLX. Bacteriological response in 93 patients was 100%(42/42 patients) in the STFX group and 88.2%(45/51 patients) in the TFLX group. Eradication of causative organisms in overall bacteriological response was 100%(48/48) in the STFX group and 91.1%(51/56) in the TFLX group. Eradication rate of S. pneumoniae was 100%(14/14) in the STFX group and 87.0%(20/23) in the TFLX group. The incidence of adverse drug reactions (ARs) was 48.4%(61/126 patients) in the STFX group and 40.5%(49/121 patients) in the TFLX group. No severe ARs were observed in either groups, indicating that STFX is well tolerated in the treatment of community-acquired pneumonia. Results suggest that a 50mg oral dose of STFX twice daily for 7 days is useful clinically in the treatment of community-acquired pneumonia.

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Sitafloxacin (STFX), a fluoroquinolone antimicrobial agent, has a broad spectrum ofactivity 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 50mg b.i.d. for RTI from PK/PD.
Clinical efficacy was 92.3%(96/104) in the 50mg b.i.d. group and 93.1%(27/29) in the 100 mg bid. group. Bacteriological efficacy was 89.1%(57/64) in the 50mg b.i.d. group and 82.4%(14/17) in the 100mg bid. 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±0.21μg/mL and 9.38±4.24μg·h/mL in the 50mg b.i.d. group, and 1.17±0.45μg/mL and 17.16±6.52μg·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 Cmax/MIC was over 5, it was 96.3%(79/82). If AUC_0-24h/MIC wasover 100, it was 96.3%(78/81).MIC₉₀ of STFX against the causative organisms in this study was 0.1μg/mL. Results suggest that 50mg b.i.d. of STFX can achieve C_max/MIC 5 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 50mg b.i.d. group and 42.4%(14/33 patients) in the 100mg b.i.d. group. The major ADR was diarrhoea (20/148, 13.5%). C_max and AUC_0-24h of patientsin 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 50mg b.i.d. of STFX is optimal in the treatment of RTI.

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The clinical efficacy and safety of sitafloxacin (STFX), a fluoroquinolone compound, in complicated urinary tract infections (UTI) was investigated in a randomized double-blind comparative study using levofloxacin (LVFX) as a control.
Patients with complicated UTI without indwelling catheters were treated orally 7 days with 50mg b.i.d. of STFX or 100 mg t.i.d. of LVFX. Clinical efficacy was evaluated based on criteria for evaluation ofclinical efficacy of antimicrobial agents on urinary tract infection (third edition).
Patients evaluated numbered 200. Overall clinical efficacy was 96.1%(98/102) in the STFX group and 82.7%(81/98) in the LVFX group. The difference in efficacy was 13.4% and the minimum 90% confidence interval was 6.4%. The noninferiority of STFX efficacy was evaluated against that of LVFX. Strains isolated before dosing numbered 280. Overall microbiological eradication was 96.4%(132/137) in the STFX group and 86.0%(123/143) in the LVFX group. Eradication in the STFX group was significantly higher than that in the LVFX group.
The incidence of adverse reactions was 24.6%(30/122) in the STFX group and 11.6%(14/121) in the LVFX group. The incidence in the STFX group was significantly higher than that in the LVFX group.(X²test: p=0.008). The most common adverse reaction was diarrhea in both groups. All symptoms were mild or moderate.
Results suggest that 50mg b.i.d. of STFX is effective and without significant safety problems in the treatment of complicated UTI.

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The clinically recommended dose of sitafloxacin (STFX), a fluoroquinolone compound, in complicated urinary
tract infections (UTI) was investigated in a randomized double-blind study.
Patients with complicated UTI without indwelling catheters were treated for 7 days with either 50 mg b.i. d.(group L) or 100 mg b.i.d.(group H) of oral STFX. Clinical efficacy was evaluated based on criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft, fourth edition).
Patients numbered 196 and overall clinical efficacy at the end of treatment was 91.0%(91/100) in group L and 96.9%(93/96) in group H. Strains isolated before dosing numbered 302 and overall microbiological eradication was 93.5%(145/155) in group L and 96.6%(142/147) in group H. Eradication for microbiological outcome at 5 to 9 days after the end of treatment was 56.3%(54/96) in group L and 63.4%(59/93) in group H. Eradication for microbiological outcome at 4 to 6 weeks after the end of treatment was 57.8%(26/45) in group L and 57.1%(32/56) in group H. The incidence of adverse reactions was 24.6%(32/130) in group L and 24.6%(31/126) in group H. The most common adverse reaction was diarrhea, with an incidence slightly higher in group H than group L. All symptoms were mild or moderate.
Results suggest that 50 mg b.i.d. of STFX is a reasonable recommended dose with good clinical efficacy and tolerability in the treatment of complicated UTI.

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The clinical efficacy and safety of sitafloxacin (STFX), a fluoroquinolone compound, were evaluated in patients with febrile complicated pyelonephritis treated orally 7 days with 100 mg b. i. d. of STFX. Clinical efficacy was evaluated at 3, 7, and 14 days based on criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (third edition).
Overall clinical efficacy at 7 days was 100%(20/20), at 3 days was 100%(20/20), and at 14 days was 64.3%(9/14). Among the 36 isolates before dosing, overall microbiological eradication was 100%(36/36) at 7 days. The incidence of adverse reactions was 45.5%(10/22), the most common of which were diarrhea and alanine aminotransferase increase. All symptoms were mild. Results suggest that STFX is a useful antibacterial agent in the treatment of febrile complicated pyelonephritis.

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The efficacy and safety of sitafloxacin (STFX), a fluoroquinolone antibacterial agent, were investigated in patients with otorhinolaryngological infections. The transferability into tissues of STFX in otorhinolaryngological field was also investigated.
1. Clinical study: STFX at 100 mg was administered twice daily for 7 days to patients with acute otitis media, acute exacerbation of the chronic otitis media, acute rhinosinusitis, and acute exacerbation of chronic rhinosinusitis. STFX at 50 mg was administered twice daily for 7 days to patients with tonsillitis, pharyngitis, and laryngitis. Overall clinical efficacy was 87.8%(43/49) in those with otitis media, 89.4%(42/47) with paranasal sinusitis, and 95.0%(19/20) with tonsillitis, pharyngitis, and laryngitis. Bacteriological elimination was 83.3%(30/36) in those with otitis media, 93.1%(27/29) with paranasal sinusitis, and 100%(12/12) with tonsillitis, pharyngitis, and laryngitis. Adverse reactions occurred in 38.5%(47/122), but all were mild to moderate.
2. Pharmacokinetic study: The ratio against simultaneous serum concentration 2.0 to 4.0 hours after a single administration of STFX at 100 mg in the middle ear mucosa was 1.4±0.7 (mean±SD), the maxillary sinus mucosa was 1.1±0.8, and the ethmoidal sinus mucosa was 1.6±0.5. STFX at 50 mg administered to the palatine tonsil was 1.8±0.4. Adverse reactions numbered 10.0%(3/30), but all were mild.
Results suggested that STFX is well transferred tissues in the otorhinolaryngological field and is useful for the treatment of STFX at 100 mg twice for 7 days in otitis media and paranasalsinusitis, and at 50 mg twice for 7 days in tonsillitis, pharyngitis, and laryngitis.

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To assess the fluoroquinolone antibacterial agent sitafloxacin (STFX) for transferability to oral tissue, efficacy, and safety in patients with dentistry and oral surgery infection, we conducted a clinical pharmacology study using STFX at 50mg per single dose and a phase III clinical study using STFX at 50mg or 100mg b. i. d. for 3 to 7 days.
1. Oral tissue concentration 2.7 to 3.7 hours after a single treatment of STFX at 50 mg in 10 cases for data analysis was 0.57±0.17μg/g in gingiva and 0.32±0.17μg/g in extraction wound fluid, making the transfer rate 1.3±0.4 in gingiva and 0.8±0.5 in extraction wound fluid.
2. Clinical efficacy was 97.6%(41/42) rated by doctors in charge, and 85.0%(34/40) by rating ratio based on the Japanese Society of Oral Therapeutics and Pharmacology on day 3 of treatment.
3. Bacteriological elimination was 100%(37/37) at the end of treatment and 94.3%(33/35) on day 3 of treatment.
4. No adverse reactions were seen in the clinical pharmacology study, but occurred in 22 (44.9%, 33 events) of 49 cases for data analysis in the clinical study; none were severe.
These results suggest that STFX is well transferred to oral tissues and useful in the treatment of odontogenic infections at a dose of 50 mg b. i. d.

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The clinical efficacy and safety of sitafloxacin (STFX), a fluoroquinolone compound, were evaluated in male patients with nongonococcal urethritis treated orally 7 days with 50 mg b.i.d. of STFX. Clinical efficacy was evaluated based on criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft, fourth edition).
Overall clinical efficacy was 88.6%(31/35) for nongonococcal urethritis and, by diagnosis, 85.2%(23/27) for nongonococcal-chlamydial urethritis, 100%(7/7) for Mycoplasma genitalium-negative nongonococcalnonchlamydial urethritis, and excellent in 1 case with M. genitalium-positive nongonococcal urethritis. Eradication by microorganism was 96.0%(24/25) for Chlamydia trachomatis, 88.9%(8/9) for Ureaplasma urealyticum, and 100%(7/7) for Ureaplasma parvum. Two of 3 strains of M. genitalium were eradicated. The incidence of adverse reactions was 27.3%(12/44), the most common being diarrhea. All symptoms were mild or moderate.
Results suggest that STFX was effective and safe in the treatment of male nongonococcal urethritis.

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The clinical efficacy and safety of sitafloxacin (STFX), a new quinolone compound, were evaluated in patients with cervicitis with Chlamydia trachomatis. STFX was administered orally at 50 mg twice a day for 7 days.
Overall clinical efficacy was 97.5%(39/40) in cervicitis. Eradication in microbiological outcome for C. trachomatis was 97.5%(39/40). Cure at the end of treatment was 32.5%(13/40) and at 1-2 weeks after the end of treatment was 47.5%(19/40).
Adverse reactions occurred in 23.3%(10/43) of cases evaluable for safety, the most common being diarrhoea at an incidence of 9.3%(4/43). All symptoms were mild or moderate.
Results suggest that STFX is effective and safe in the treatment of cervicitis with C. trachomatis.

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The clinical efficacy and safety of sitafloxacin (STFX), a new quinolone compound, were evaluated in male patients with gonococcal urethritis by preliminary study. STFX was orally administered at a single dose of 200 mg. Clinical efficacy was evaluated based on the criteria for evaluation of clinical efficacy of antimicrobial agents on urinary tract infection (draft, fourth edition).
Overall clinical efficacy was 75.0%(9/12) in gonococcal urethritis. The range of MICs of STFX against 12 Neisseria gonorrhoeae isolates from this study was≤0.001 to 0.25μg/mL, and MICs of 3 isolates were 0.25μg/mL. Overall eradication was 75.0%(9/12) for N. gonorrhoeae. Eradication by MICs was 100%(8/8) with MIC of≤0.06 p emL, and 25.0%(1/4) with MIC of≤0.12μg/mL.
MICs of ciprofloxacin against 7 of 12 isolates were≤1μg/mL. These 7 isolates had amino acid substitutions in quinolone-resistance-determining regions of GyrA and ParC. Four of 7 strains with quinolone resistance were eradicated. Adverse reactions occurred in 25.0%(3/12) of cases evaluable for safety. Adverse reactions involved diarrhea, headache, and blood bilirubin increase in one case each. All symptoms were mild.
Results suggest that STFX at a single dose of 200 mg is inadequate in dosage for eradicating quinoloneresistant N. gonorrhoeae, but safe in the treatment of male gonococcal urethritis.

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We studied the pharmacokinetics of sitafloxacin (STFX) in healthy male volunteers given single oral doses 25 mg, 50 mg, 100 mg (fasting and non fasting state), or 200 mg. Non compartmentalanalysis was used to calculate pharmacokinetic parameters of STFX. C_max of 0.29, 0.51, 1.00, 0.88, and 1.86 of serum appeared within 1 to 2 h after administration. After C_max was reached, serum drug levels decreased with elimination half-lives of 5 to 6 h. C_max and AUC_0-inf increased in a dose proportional manner. We found a goodlinear correlation between administered doses and resulting C_max and AUC_0-inf. Food intake did not significantly influence STFX pharmacokinetics.

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