Abstract
The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily (50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC0–24h divided by the minimum inhibitory concentration (MIC) (fAUC0–24h/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C peak divided by the MIC (fC peak/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC0–24h/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC peak/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C peak is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.
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Acknowledgments
Based on the results of this study, the clinical use of 100 mg once daily was approved, in addition to the original dose regimen, in Japan in August 2010. This work received financial support from Daiichi Sankyo Co., Ltd., Tokyo, Japan. We thank Daiichi Sankyo Co., Ltd., Tokyo, Japan, for providing editorial assistance.
Conflict of interest
Dr. Kohno has received honoraria for speaking and grant support from Daiichi Sankyo Co., Ltd. Dr. Niki has received speaker’s honoraria and an endowed chair from Daiichi Sankyo Co., Ltd. Dr. Yanagihara has received speaker’s honoraria from Daiichi Sankyo Co., Ltd. Dr. Kaku has received speaker’s honoraria from Daiichi Sankyo Co., Ltd. Dr. Watanabe has received speaker’s honoraria and an endowed chair from Daiichi Sankyo Co., Ltd. Dr. Aoki has received speaker’s honoraria from Daiichi Sankyo Co., Ltd. Dr. Hori has received speaker’s honoraria from Daiichi Sankyo Co., Ltd. Dr. Fujita has received speaker’s honoraria and grant support from Daiichi Sankyo Co., Ltd. All other authors report no conflicts of interest.
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Kohno, S., Niki, Y., Kadota, Ji. et al. Clinical dose findings of sitafloxacin treatment: pharmacokinetic–pharmacodynamic analysis of two clinical trial results for community-acquired respiratory tract infections. J Infect Chemother 19, 486–494 (2013). https://doi.org/10.1007/s10156-012-0543-z
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DOI: https://doi.org/10.1007/s10156-012-0543-z