Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects

• Published in: Journal of antimicrobial chemotherapy Vol. 51; no. 3; pp. 727 - 730
• Main Authors: Andrews, J., Honeybourne, D., Jevons, G., Boyce, M., Wise, R., Bello, A., Gajjar, D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2003; Oxford Publishing Limited (England)
• Subjects: Administration, Oral; Adult; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Bronchi - drug effects; Bronchi - metabolism; Bronchoalveolar Lavage Fluid; concentrations; Female; Fluoroquinolones; garenoxacin; Humans; Indoles - administration & dosage; Indoles - blood; Indoles - pharmacokinetics; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - metabolism; Male; Medical sciences; Pharmacology. Drug treatments; Quinolones - administration & dosage; Quinolones - blood; Quinolones - pharmacokinetics; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; respiratory tree; Human; Respiratory tract; In vivo; Antibiotic; Healthy subject; Distribution; Single dose; Oral administration; Bronchus; Antibacterial agent; Pharmacokinetics
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkg110

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 MIC90s 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.