Spiramycin uptake by alveolar macrophages.

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.