Skip to main content

Clinical dose findings of sitafloxacin treatment: pharmacokinetic–pharmacodynamic analysis of two clinical trial results for community-acquired respiratory tract infections

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.

This is a preview of subscription content, access via your institution.

References

  1. Craig WA. Does the dose matter? Clin Infect Dis. 2001;33(suppl 3):S233–7.

    PubMed  Article  CAS  Google Scholar 

  2. Saito A, Tanigawara Y, Watanabe A, Aoki N, Niki Y, Kohno S, et al. Open study of sitafloxacin in patients with respiratory tract infections—PK/PD study (in Japanese). Jpn J Chemother. 2008;56(S-1):63–80.

    Google Scholar 

  3. Yamaguchi K, Ohno A, Ishii Y, Tateda K, Iwata M, Kanda M, et al. In vitro susceptibilities to levofloxacin and various antibacterial agents of 18,639 clinical isolates obtained from 77 centers in 2004 (in Japanese). Jpn J Antibiot. 2006;59:428–51.

    PubMed  Article  Google Scholar 

  4. Yamaguchi K, Ohno A, Ishii Y, Tateda K, Iwata M, Kanda M, et al. In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007 (in Japanese). Jpn J Antibiot. 2009;62:346–70.

    PubMed  CAS  Google Scholar 

  5. Wikler MA, Low DA, Cookerill FR, Sheehan DJ, Craig WA, Tenover FC, et al. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. Seventh edition. CLSI (NCCLS). 2006;26:M7–A7.

    Google Scholar 

  6. Blondeau JM, Zhao X, Hansen G, Drlica K. Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2001;45:433–8.

    PubMed  Article  CAS  Google Scholar 

  7. Saito A, Miki F, Oizumi K, Rikitomi N, Watanabe A, Koga H, et al. Clinical evaluation methods for new antimicrobial agents to treat respiratory infections: report of the Committee for the Respiratory System, Japan Society of Chemotherapy. J Infect Chemother. 1999;5:110–23.

    PubMed  Article  Google Scholar 

  8. Japanese Society of Chemotherapy. Criteria for assessment of adverse reactions and abnormal laboratory values associated with antimicrobial agents in study subjects (in Japanese). Jpn J Chemother. 1991;39:687–9.

    Google Scholar 

  9. Japanese Society of Chemotherapy. About the partial modification of ‘‘Criteria for assessment of adverse reactions and abnormal laboratory values associated with antimicrobial agents in study subjects” (in Japanese). Jpn J Chemother. 1995;43 (opening article).

  10. Mouton JW, Dudley MN, Cars O, Derendorf H, Drusano GL. Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs. Int J Antimicrob Agents. 2002;19:355–8.

    Google Scholar 

  11. Matsumoto T, Uchino K, Yamaguchi H, et al. Study on the safety and efficacy of sitafloxacin: results of the use-results survey (in Japanese). Jpn J Antibiot. 2011;64:319–37.

    PubMed  Google Scholar 

  12. Hsueh PR. Study for monitoring antimicrobial resistance trends (SMART) in the Asia-Pacific region, 2002–2010. Int J Antimicrob Agents. 2012;40(S1):S1–3.

    PubMed  Article  CAS  Google Scholar 

  13. Tiengrim S, Phiboonbanakit D, Thunyaharn S, Tantisiriwat W, Santiwatanakul S, Susaengrat W, et al. Comparative in vitro activity of sitafloxacin against bacteria isolated from Thai patients with urinary tract infections and lower respiratory tract infections. J Med Assoc Thai. 2012;95(S2):S6–17.

    PubMed  Google Scholar 

  14. Yamaguchi K, Ohno A, Ishii Y, Tateda K, Iwata M, Akizawa H, et al. In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,866 clinical isolates obtained from 72 centers in 2010 (in Japanese). Jpn J Antibiot. 2012;65:181–206.

    PubMed  CAS  Google Scholar 

  15. Nakashima M, Uematsu T, Kosuge K, Umemura K, Hakusui H, Tanaka M. Pharmacokinetics and tolerance of DU-6859a, a new fluoroquinolone, after single and multiple oral doses in healthy volunteers. Antimicrob Agents Chemother. 1995;39:170–4.

    PubMed  Article  CAS  Google Scholar 

  16. Keating GM. Sitafloxacin: in bacterial infections. Drugs. 2011;71(6):731–44.

    PubMed  Article  CAS  Google Scholar 

  17. Kawada Y, Ishihara S, Matsui T, Tsugawa M, Matsumoto T, Watanabe K, et al. Comparative study on sitafloxacin and levofloxacin in complicated urinary tract infections (in Japanese). Jpn J Chemother. 2008;56(S-1):81–91.

    Google Scholar 

  18. Kawada Y, Yasuda M, Tanaka K, Monden K, Akasaka S, Egashira T, et al. Dose-comparative study of sitafloxacin in complicated urinary tract infections (in Japanese). Jpn J Chemother. 2008;56(S-1):92–102.

    Google Scholar 

  19. Baba S, Suzuki K, Yamanaka N, Yamashita H, Kurono Y, Hori S. Efficacy and safety of sitafloxacin in patients with otorhinolaryngological infections and its tissue distribution in the otorhinolaryngological field (in Japanese). Jpn J Chemother. 2008;56(S-1):110–20.

    CAS  Google Scholar 

  20. Sasaki J, Hori S. Oral tissue distribution, efficacy, and safety of sitafloxacin in patients with dentistry and oral surgery infection (in Japanese). Jpn J Chemother. 2008;56(S-1):121–9.

    CAS  Google Scholar 

  21. Kawada Y, Matsumoto T, Onodera S, Kaku M, Hori S. Clinical study of sitafloxacin in male nongonococcal urethritis (in Japanese). Jpn J Chemother. 2008;56(S-1):130–8.

    Google Scholar 

  22. Matsuda S, Noguchi M, Yasuda J, Hori S. Clinical study of sitafloxacin in treatment of cervicitis with Chlamydia trachomatis (in Japanese). Jpn J Chemother. 2008;56(S-1):139–45.

    Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shigeru Kohno.

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10156-012-0543-z

Keywords

  • Fluoroquinolone
  • Randomized study
  • Pneumococci