Using the Satoh-Heimdahl method, we inoculaed
Streptococcus milleri NCTC 7331 and
Bacteroides fragilis NCTC 9343 into the mandibles of NZW rabbits to prepare a model of infection. We compared the tissue penetration of clarithromycin (CAM), a newly developed macrolide antibiotic, after oral administration in this animal model and in normal rabbits, which served as control. Concentrations of CAM in oral-cavity fluids and sites, including serum, tongue, gingiva, submandibular gland, parotid gland, submandibular lymph node, mandible, maxilla, and pus, were determined by bioassay.(
14C) CAM (20mg/kg) was administered into the auricular veins of infected and normal animals. Macroautoradiograms were taken 5 minutes after the intravenous injection of CAM. The following results ware obtained:
1) In the infected group, peak serum levels of CAM (0.32μg/ml) were obtained 0.75 hour after oral adminstration. Peak tissue levels of CAM (0.68-2.39μg/g) were attained 0.5-1 hour after treatment. The ratio of the peak oral tissue level to the peak serum level ranged from 2.31 to 7.47. One hour after treatment, the peak level of CAM in pus (0.1μg/ml) was obtained, and the ratio of the peak pus: serum level was 0.31.
2) In the normal group, peak serum levels of CAM (0.16μg/ml) were obtained 0.5 hour after treatment. Peak tissue levels of CAM (0.19-1.05μg/g) were obtained 0.5-2 hours after treatment. The ratio of the peak oral tissue level to the peak serum level ranged from 1.19 to 6.56.
3) In the infected group, macroautoradiograms disclosed an area with comparatively high radioactivity exceeding the blood CAM level, particularly around the focus of infection.
4) The results of bioassay showed, high radioactivity primarily in submandibular gland tissue and in the submandibular lymph nodes in both the infected group and the normal group.
In general, the tissue levels of macrolides are higher than their blood levels. The results of the present experiment with CAM are consistent with this finding. High concentration of CAM were selectively distributed around sites of infection in the jaw bones; CAM can therefore exert its inherent antibiotic effect.
抄録全体を表示