JAC Advance Access originally published online on July 10, 2007
Journal of Antimicrobial Chemotherapy 2007 60(3):677-680; doi:10.1093/jac/dkm242
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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
1 Department of Medical Microbiology, City Hospital NHS Trust, Birmingham, UK 2 Department of Respiratory Medicine, Heartlands NHS Trust, Birmingham, UK 3 Hammersmith Medicines Research Ltd, Central Middlesex Hospital, London, UK 4 Arpida, Reinach, Switzerland
Received 6 February 2007; returned 13 April 2007; revised 15 May 2007; accepted 11 June 2007
* Corresponding author. Tel: +44-121-507-5693; Fax: +44-121-507-5521; E-mail: jenny.andrews{at}swbh.nhs.uk
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 0.24 mg/L (SD 0.05), 0.35 mg/kg (SD 0.17), 7.16 mg/L (SD 1.91) and 6.38 mg/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 MIC90 for penicillin-susceptible Streptococcus pneumoniae (MIC90 0.06 mg/L), penicillin-intermediate S. pneumoniae (MIC90 2 mg/L), penicillin-resistant S. pneumoniae (MIC90 4 mg/L) for 7, 7 and 4 h, respectively, and Chlamydia pneumoniae (MIC90 0.5 mg/L) for 7 h. Mean iclaprim concentrations in ELF exceeded the MIC90 for Haemophilus influenzae (MIC90 4 mg/L) and Moraxella catarrhalis (MIC90 8 mg/L) for up to 4 and 2 h, respectively; in AM the MIC90 was exceeded for up to 7 h. Furthermore, the MIC90 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.
Keywords: diaminopyrimidine , concentration , respiratory tree
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