Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study

Yasuhiro Umezaki, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Yuki Enoki, Akari Shigemi, Erika Watanabe, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa, Yasuo Takeda

研究成果: Article査読

抄録

The bacterium Pseudomonas aeruginosa is known to be associated with nosocomial infections around the world. Pazufloxacin, a potent DNA gyrase inhibitor, is known to be an effective drug candidate. However, it has not been clarified whether the pharmacokinetic (PK)/pharmacodynamic (PD) of pazufloxacin was effective against P. aeruginosa. Herein, we demonstrated that the PK/PD index of pazufloxacin against P. aeruginosa infection is used to optimize the dosing regiments. We constructed an in vivo infection model by infecting P. aeruginosa into the thigh of a mouse to determine the PD, and we measured the serum concentration of pazufloxacin to construct the PK model using high-performance liquid chromatography. The therapeutic efficacy of pazufloxacin was correlated with the ratio of the area under the free concentration time curve at 24 h to the minimum inhibitory concentration (fAUC24/MIC), and the maximum free concentration to the MIC (fCmax/MIC). Each contribution rate (R2) was 0.72 and 0.65, respectively, whereas the time at which the free drug concentration remained above the MIC (R2 = 0.28). The target value of pazufloxacin fAUC24/MIC for stasis was 46.1, for 1 log10 it was 63.8, and for 2 log10 it was 100.8. Moreover, fCmax/MIC for stasis was 5.5, for 1 log10 it was 7.1, and for 2 log10 it was 10.8. We demonstrated that the in vivo concentration-dependent activity of pazufloxacin was effective against the P. aeruginosa infection, and successfully made the PK/PD model sufficiently bactericidal. The PK/PD model will be beneficial in preventing the spread of nosocomial infections.

本文言語English
論文番号982
ジャーナルAntibiotics
11
7
DOI
出版ステータスPublished - 2022 7月
外部発表はい

ASJC Scopus subject areas

  • 微生物学
  • 生化学
  • 薬理学、毒性学および薬学(全般)
  • 微生物学(医療)
  • 感染症
  • 薬理学(医学)

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