Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men
| Autor: | S. Warrington, P. Fry, David Honeybourne, Richard J. S. Wise, G. Jevons, Adam P. Fraise, S. Hawser, J. M. Andrews, J. P. Ashby |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Microbiology (medical) Bacillus Bronchi Microbial Sensitivity Tests Respiratory Mucosa Pharmacology medicine.disease_cause Epithelium Group B Haemophilus influenzae Microbiology Pharmacokinetics Bronchoscopy Macrophages Alveolar Streptococcus pneumoniae medicine Humans Pharmacology (medical) Infusions Intravenous Antibacterial agent business.industry Anti-Bacterial Agents Penicillin Pyrimidines Infectious Diseases medicine.anatomical_structure Iclaprim Folic Acid Antagonists Pulmonary alveolus business medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy. 60:677-680 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkm242 |
| Popis: | Objectives: A validated microbiological assay was used to measure concentrations of iclaprim (AR-100) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF) after a single 1.6 mg/kg intravenous 60 min iv infusion of iclaprim. Methods: Male volunteers were randomly allocated to three nominal sampling time intervals 1-2 h (Group A), 3-4 h (Group B) and 5.5-7.0 h (Group C) after the start of the drug infusion. Results: Mean iclaprim concentrations in plasma, BM, AM and ELF, respectively, were for Group A 0.59 mg/L (SD 0.18), 0.51 mg/kg (SD 0.17), 24.51 mg/L (SD 21.22) and 12.61 mg/L (SD 7.33); Group B 0.24mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38mg/L (SD 5.17); and Group C 0.14 mg/L (SD 0.05), no detectable level in BM, 5.28 mg/L (SD 2.30) and 2.66 mg/L (SD 2.08). Conclusions: Iclaprim concentrations in ELF and AM exceeded the MIC 90 for penicillin-susceptible Streptococcus pneumoniae (MIC 90 0.06mg/L), penicillin-intermediate S. pneumoniae (MIC 90 2mg/L), penicillin-resistant S. pneumoniae (MIC 90 4 mg/L) for 7,7 and 4 h, respectively, and Chlamydia pneumoniae (MIC 90 0.5mg/L) for 7h. Mean iclaprim concentrations in ELF exceeded the MIC 90 for Haemophilus influenzae (MIC 90 4 mg/L) and Moraxella catarrhalis (MIC 90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC 90 was exceeded for up to 7 h. Furthermore, the MIC 90 for methicillin-resistant Staphylococcus aureus of 0.12 mg/L was exceeded at all sites for up to 7 h. These data suggest that iclaprim reaches lung concentrations that should be effective in the treatment of community-acquired pneumonia. |
| Databáze: | OpenAIRE |
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