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Spiramycin uptake by alveolar macrophages
R Harf1, G Panteix, J F Desnottes
1Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
Abstract:
The in-vitro and in-vivo uptake of spiramycin by human and animal alveolar macrophages was studied. In-vitro penetration was studied in guinea pig and human alveolar macrophages incubated in medium 199 at 37 degrees C containing spiramycin at various concentrations. Results were expressed as the cellular/extracellular concentration ratio (C/E). The in-vivo study was performed in patients receiving 500 or 1000 mg spiramycin every 8 h as a 1-h infusion on day 1. A single infusion was given on day 2, 2 h before serum and bronchoalveolar lavage (BAL) sampling. Spiramycin was assayed by HPLC, and by a microbiological assay. In guinea pig alveolar macrophages, the C/E ratio of spiramycin after 60 min at 37 degrees C was 20.3 +/- 6.5 when the concentration was 10 mg/l. In human alveolar macrophages, the C/E ratio was 21.3 +/- 8.7 at 5 mg/l spiramycin and 23.8 +/- 8.7 at 50 mg/l. The accumulated spiramycin was slowly released when the cells (guinea pig alveolar macrophages) were washed and re-incubated in antibiotic free medium. Spiramycin was able to penetrate the alveolar space. In BAL supernatant, spiramycin levels were about 24-fold the serum level (n = 6 patients), when the BAL/serum glucose ratios were used as the dilution estimate. Alveolar macrophage levels ranged from 17 to 210 mg/l (n = 6 patients receiving 500 mg spiramycin infusion). These results are consistent with the in-vitro data.
Insights
Spiramycin effectively penetrates human and animal alveolar macrophages, reaching high concentrations within lung tissues. This antibiotic demonstrates significant uptake and sustained presence in the alveolar space, supporting its use in respiratory infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Pulmonology
Background:
- Alveolar macrophages play a crucial role in lung defense.
- Understanding antibiotic penetration into macrophages is vital for treating respiratory infections.
Purpose of the Study:
- To investigate the in-vitro and in-vivo uptake of spiramycin by human and animal alveolar macrophages.
- To determine spiramycin's penetration into the alveolar space and its concentration within macrophages.
Main Methods:
- In-vitro studies using guinea pig and human alveolar macrophages incubated with spiramycin.
- In-vivo studies in patients receiving spiramycin infusions, with serum and bronchoalveolar lavage (BAL) sampling.
- Spiramycin quantification using High-Performance Liquid Chromatography (HPLC) and microbiological assays.
Main Results:
- High cellular/extracellular (C/E) concentration ratios for spiramycin were observed in both guinea pig (20.3) and human (21.3-23.8) alveolar macrophages.
- Spiramycin demonstrated slow release from macrophages after initial uptake.
- In vivo, BAL supernatant spiramycin levels were approximately 24-fold higher than serum levels, with macrophage levels ranging from 17 to 210 mg/l.
Conclusions:
- Spiramycin exhibits excellent penetration into alveolar macrophages.
- The drug accumulates significantly within the alveolar space, supporting its therapeutic potential for lung infections.