Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases.
BACKGROUND
The recognition that periodontal diseases are associated with specific pathogens has led to interest in the use of antibacterial drugs for inhibition of these microorganisms. On these bases, the present study was aimed at evaluating the tissue distribution of the new macrolide antibiotic azithromycin in patients subjected to oral surgery for chronic inflammatory diseases of both marginal and periapical periodontium.


METHODS
Thirty-two patients were treated with azithromycin 500 mg/day orally for 3 consecutive days, and drug concentrations in plasma, saliva, normal gingiva, and pathological periodontal tissues were evaluated. For this purpose, samples of blood, saliva, normal gingiva, granulation tissue, and radicular granuloma or cyst wall (from dentigerous cyst) were collected during oral surgery or 0.5, 2.5, 4.5, and 6.5 days after the end of pharmacological treatment; then, azithromycin levels were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the indicator organism.


RESULTS
The concentrations of azithromycin in plasma, saliva, normal gingiva, and pathological tissues reached the highest values 12 hours after the last dose (0.37+/-0.05 mg/l, 2.12+/-0.30 mg/l, 6.30+/-0.68 mg/kg, and 11.60+/-1.50 mg/kg, respectively) and then declined gradually. Consistent levels of the drug in normal gingiva and pathological tissues could be detected, however, up to 6.5 days, indicating that azithromycin was retained in target tissues for a long time after the end of treatment. Moreover, azithromycin levels in both normal gingiva and pathological tissues exceeded the minimum inhibitory concentrations of most pathogens involved in the pathophysiology of chronic inflammatory periodontal diseases. Notably, azithromycin levels in pathological tissues were significantly higher than those in normal gingiva 0.5, 2.5, and 4.5 days after the last dose.


CONCLUSIONS
The present results indicate a marked penetration of azithromycin into both normal and pathological periodontal tissues, suggesting that azithromycin represents a promising option in both adjunctive and prophylactic treatments of chronic inflammatory periodontal diseases.
Blandizzi
C
C
Dipartimento di Oncologia, Divisione di Farmacologia e Chemioterapia, Universitá di Pisa, Italy.
Malizia
T
T
Lupetti
A
A
Pesce
D
D
Gabriele
M
M
Giuca
M R
MR
Campa
M
M
Del Tacca
M
M
Senesi
S
S
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017963:Azithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002908:Chronic Disease; D003803:Dentigerous Cyst / Q000378:metabolism / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005881:Gingiva / Q000378:metabolism; D006097:Granulation Tissue / Q000378:metabolism; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008837:Micrococcus / Q000187:drug effects; D008875:Middle Aged; D010484:Periapical Granuloma / Q000378:metabolism / Q000601:surgery; D010485:Periapical Periodontitis / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D010486:Periapical Tissue / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D010519:Periodontium / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D017963:Azithromycin