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学科主题: 临床医学
题名:
Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection
作者: Xiao, Xiu-mei2; Xiao, Yong-hong1
关键词: antofloxacin hydrochloride ; PK/PD ; murine thigh infection model ; Staphylococcus aureus ; AUC(24h)/MIC
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2008-10-01
DOI: 10.1111/j.1745-7254.2008.00872.x
卷: 29, 期:10, 页:1253-1260
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: STREPTOCOCCUS-PNEUMONIAE ; MOUSE MODEL ; PHARMACODYNAMICS ; CIPROFLOXACIN ; LEVOFLOXACIN ; FLUOROQUINOLONES ; PARAMETERS
英文摘要:

Aim: Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad-spectrum in vitro activity. Using the neutropenic murine thigh infection model, we defined the pharmacodynamic profile and property of antofloxacin hydrochloride against Staphylococcus aureus. Methods: Single-dose pharmacokinetic studies of antofloxacin hydrochloride were carried out in thigh infected mice. Therapy was initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for different dosing regimens. The thighs were removed for bacterial measurement after 24 h of therapy, the best pharmacokinetic/pharmacodynamic (PK/PD) index correlated with the efficacy was determined by nonlinear regression analysis. A sigmoid E-max dose-response model was used to estimate the daily dose and AUC(24 h)/MIC (minimal inhibitory concentration) required to achieve a static effect. Results: The PK was linear with similar elimination half-life over the dose range studied. The AUC(24 h)/MIC ratio was the PK/PD parameter that best correlated with efficacy (R-2=923%, 90.8% for the two organisms, compared with C-max/MIC and T > MIC [%], respectively). The 24 h static dose ranged from 34.3 to 153.7 mg/kg per d for all S aureus strains, the total AUC(24 h)/MIC ratio to achieve bacteriostatic effect varied from 31.7 to 122.5 (mean, 65.7 +/- 30.6). Conclusion: Antofloxacin hydrochloride showed powerful antibacterial activity against the S aureus isolates used in our neutropenicinfected mice model. Our data suggested that the AUC/MIC ratio appeared to be most closely linked to the bacterial outcome (R-2 > 90%), and a total AUC(24 h)/MIC ratio of 65.7 appears to be the target value to achieve a net bactericidal activity against S aureus, similar to the results of other fluoroquinolones.

语种: 英语
WOS记录号: WOS:000259937500016
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51110
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 3, Dept Lab Med, Beijing 100083, Peoples R China

Recommended Citation:
Xiao, Xiu-mei,Xiao, Yong-hong. Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection[J]. ACTA PHARMACOLOGICA SINICA,2008,29(10):1253-1260.
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