title: Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.
abstract: A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.
authors.affiliation: Department of Medical Microbiology, City Hospital NHS Trust, Birmingham, UK. Jenny.Andrews@cityhospbham.wmids.nhs.uk
authors.forename: J
authors.initials: J
authors.lastname: Andrews
authors.forename: D
authors.initials: D
authors.lastname: Honeybourne
authors.forename: G
authors.initials: G
authors.lastname: Jevons
authors.forename: M
authors.initials: M
authors.lastname: Boyce
authors.forename: R
authors.initials: R
authors.lastname: Wise
authors.forename: A
authors.initials: A
authors.lastname: Bello
authors.forename: D
authors.initials: D
authors.lastname: Gajjar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015363:Quinolones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D024841:Fluoroquinolones; D007211:Indoles; D015363:Quinolones; C419689:garenoxacin