Pharmacokinetics/pharmacodynamics of antofloxacin hydrochloride in a neutropenic murine thigh model of Staphylococcus aureus infection

$48.00 plus tax (Refund Policy)

Download / Buy Article:

Abstract:

Abstract

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 Emax dose-response model was used to estimate the daily dose and AUC24 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 AUC24 h/MIC ratio was the PK/PD parameter that best correlated with efficacy (R2=923%, 90.8% for the two organisms, compared with Cmax/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 AUC24 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 (R2>90%), and a total AUC24 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.

Keywords: AUC24h/MIC; PK/PD; Staphylococcus aureus; antofloxacin hydrochloride; murine thigh infection model

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2008.00872.x

Affiliations: Department of Laboratory Medicine, Peking University Third Hospital, Beijing 100083

Publication date: October 1, 2008

Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more