Abstract
An optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (PK–PD) analysis in patients with community-acquired respiratory tract infections (RTI). A population pharmacokinetic analysis of sitafloxacin was conducted using clinical data of five clinical pharmacology studies and one clinical PK–PD study in patients with RTIs. The pharmacokinetic parameters in individual patients were estimated by the Bayesian method to examine any correlation between pharmacokinetics and bacteriological efficacy. Efficacy data were obtained from the clinical PK–PD study, in which 50 or 100 mg sitafloxacin was administered twice daily for 7 days. In addition, an efficacy was simulated for a hypothetical dose regimen of 100 mg once daily. The fAUC0–24h/MIC and the fC max/MIC of sitafloxacin at a dose of 50 mg twice daily were 117.5 ± 78.0 and 7.3 ± 4.7 (mean ± SD), respectively. As a result of the univariate logistic regression analysis, the larger the value of fAUC0–24h/MIC or fC max/MIC becomes, the higher the bacteriological efficacies. The eradication rates for fAUC0–24h/MIC ≥ 30 and for fC max/MIC ≥ 2 were 96.4 % and 96.3 %, respectively. The PK–PD target values of sitafloxacin for the treatment of mild to moderate RTIs were considered to be fAUC0–24h/MIC ≥ 30 and fC max/MIC ≥ 2. The PK–PD parameters at the regimen of 50 or 100 mg twice daily in patients with RTIs reached the target values. Furthermore, a 100 mg once-daily regimen was expected to show similar efficacy based on the PK–PD simulations.
Highlights
Sitafloxacin, ((-)-7-[(7S)-7-amino-5-azaspiro[2.4]hept5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]1,4-dihydro-4-oxo-3-quinolinecarboxylic acid), is a fluoroquinolone antimicrobial agent developed by Daiichi Sankyo Co., Ltd. in Japan
An optimal dosage regimen of sitafloxacin was considered based on a pharmacokinetics and pharmacodynamics (PK–PD) analysis in patients with communityacquired respiratory tract infections (RTI)
CLt/F appeared to be proportional to CLcr with the population mean ratio of 2.58 and was 1.27 times higher in healthy volunteers than patients with RTIs
Summary
Sitafloxacin, ((-)-7-[(7S)-7-amino-5-azaspiro[2.4]hept5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]1,4-dihydro-4-oxo-3-quinolinecarboxylic acid), is a fluoroquinolone antimicrobial agent developed by Daiichi Sankyo Co., Ltd. in Japan. Sitafloxacin has a broad-spectrum antimicrobial activity against aerobic, anaerobic, gram-positive, and gram-negative bacteria, as well as Mycoplasma spp. and Chlamydia spp. It has a higher antimicrobial activity than other quinolones against many pathogenic organisms [1, 2]. According to several clinical pharmacology studies that have been already reported [3,4,5,6], sitafloxacin was rapidly absorbed after oral administration and has a high bioavailability (89 %). The cumulative urinary excretion of unchanged sitafloxacin within 48 h after administration is approximately 70 % of
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