Clinical studies of garenoxacin.
Garenoxacin mesylate hydrate (GRN) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. It has favourable pharmacokinetic profiles for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), with good penetration into sputum and otorhinolaryngological tissues. In clinical studies, the efficacy of GRN ranged from 92% to 96% in patients with bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia and acute bronchitis. Efficacy was 85% in acute infectious exacerbations of chronic respiratory disease and ranged from 81% to 95% in otorhinolaryngological infections. Bacterial eradication was 90.9% for Staphylococcus aureus, 99.2% for Streptococcus pneumoniae, 98.2% for Haemophilus influenzae, 96.6% for Moraxella catarrhalis, 100% for penicillin-resistant S. pneumoniae, 100% for beta-lactamase-negative ampicillin-resistant H. influenzae and beta-lactamase-positive H. influenzae, and 96.2% for beta-lactamase-positive M. catarrhalis. Garenoxacin concentrations in plasma and tissues using GRN 400mg once a day were higher than the MIC90 (minimum inhibitory concentration for 90% of the organisms) of major causative pathogens. The trough concentration (Cmin) in plasma was 1.92 microg/mL, a level that was higher than the mutant prevention concentration, suggesting that GRN is unlikely to induce the selection of resistant strains during treatment. In clinical studies, GRN did not produce class adverse effects of fluoroquinolones such as QTc prolongation, blood glucose abnormality or severe liver damage. No serious adverse events were observed during the trials. The results indicate that GRN is very effective in treating patients with upper and lower respiratory tract infections.
Takagi
Hiroyasu
H
Clinical Research Department, Toyama Chemical Co., Ltd., 4-1, Shimookui 2-chome, Toyama 930-8508, Japan. hiroyasu_takagi@toyama-chemical.co.jp
Tanaka
Kiyoshi
K
Tsuda
Hisatsugu
H
Kobayashi
Hiroyuki
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D017326:Clinical Trials, Phase III as Topic; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000382:microbiology
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C419689:garenoxacin