Evaluation of the effects of ambroxol on the ofloxacin concentrations in bronchial tissues in COPD patients with infectious exacerbation.
Infectious excerbations of COPD are generally due to Streptococcus pneumoniae, Haemophilus species, and other Gram-negative bacteria. Ofloxacin has potent activity against Gram-negative species but is less effective against Gram-positive species including Streptococcus pneumoniae. It has also been shown that the administration of ambroxol increases the concentration of some antibiotics in pulmonary tissues. The aim of the study was to determine whether ambroxol increases the bronchial tissue concentrations of ofloxacin to a level exceeding the MIC90 of the bacterial species less susceptible to ofloxacin. 24 patients with COPD were randomized in two groups. Drug regimens of ofloxacin alone (200 mg twice daily) or ofloxacin (200 mg twice daily)+ambroxol (30 mg thrice daily) were administered over 10 d. A fibroscopy was performed on day 10 with bronchial biopsies and broncho-alveolar lavage. At steady state, concentrations of drug in plasma and bronchial samples were assayed by HPLC with fluorometric detection. There was no significant difference in the bronchial levels of ofloxacin between the two groups; however, in alveolar cells, ofloxacin concentration was three times higher in the group with ambroxol. Ambroxol does not increase ofloxacin concentrations in bronchial tissue because high concentrations are already present in the lung.
Département des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Université de Montpellier I, France.
F
F
Paganin
O
O
Bouvet
P
P
Chanez
D
D
Fabre
M
M
Galtier
P
P
Godard
F B
FB
Michel
F
F
Bressolle
D000284:Administration, Oral; D000368:Aged; D000551:Ambroxol / Q000008:administration & dosage / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D001999:Bronchoscopy; D002851:Chromatography, High Pressure Liquid; D005100:Expectorants / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013296:Streptococcus pneumoniae / Q000187:drug effects; D014018:Tissue Distribution
D000890:Anti-Infective Agents; D005100:Expectorants; D000551:Ambroxol; D015242:Ofloxacin