Proposed Pharmacokinetic-Pharmacodynamic Breakpoint of Garenoxacin and Other Quinolones

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Abstract

<p>The pharmacokinetic–pharmacodynamic (PK–PD) breakpoints (BPs) of garenoxacin (GRNX) and other oral quinolones were calculated using Monte Carlo simulation (MCS) based on the distribution of changes in their plasma concentrations. PK–PD BPs of 400 mg once a day (QD) of GRNX for the free area under the curve/minimum inhibitory concentration (fAUC/MIC) for 30 strains of Streptococcus pneumoniae and 100 strains of gram-negative bacteria (G [－]) were 0.5 and 0.125 μg/mL, respectively. PK–PD BPs of other quinolones for S. pneumoniae/G (－) were 1/0.25 μg/mL for levofloxacin (LVFX) 500 mg QD, 0.5/0.125 μg/mL for moxifloxacin (MFLX) 400 mg QD, 0.0625/0.0156 μg/mL for sitafloxacin (STFX) 50 mg twice a day (BID) (100 mg QD), and 0.125/0.0313 μg/mL for STFX 100 mg BID. We also investigated the hypothetical probability of target attainments (PTAs) of fAUC/MIC for community-acquired pneumonia (CAP) using MCS, in consideration of the isolation frequencies of the three main causative pathogens of CAP: S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. For hypothetical CAP in adults, PTA of fAUC/MIC was 100% with GRNX and MFLX, 96%–97% with STFX at 100 mg BID, 45%–46% with LVFX, and 53%–58% with STFX at 100 mg QD and 50 mg BID. Based on the PK–PD BP, GRNX showed higher fAUC/MIC than the other quinolones tested against the three main pathogens of respiratory infections.</p>

Journal

  • Japanese Journal of Infectious Diseases

    Japanese Journal of Infectious Diseases 70 (6), 616-620, 2017

    National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee

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