Azithromycin Concentrations in Blood and Gingival Fluid after Systemic Administration

Objectives: Azithromycin is a macrolide antibiotic that is active against several periodontal pathogens. Macrolides are taken up and concentrated inside gingival fibroblasts and neutrophils, which could influence their pharmacokinetics. We hypothesized that steady-state levels of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum. Methods: To test the hypothesis, four healthy subjects received an initial 500 mg dose of azithromycin followed by 250 mg doses at 24 and 48 hours. Serum and GCF samples were obtained 2, 48, and 120 hours after the final dose. GCF samples were collected with paper strips, pooled and eluted with cold ultrapure water. After extraction with diethyl ether, the azithromycin content of the serum samples and GCF eluates was determined with an agar diffusion bioassay. Results: At the 2, 48 and 120 hour time points after the final dose, the serum concentrations of azithromycin were 0.22 ± 0.02, 0.08 ± 0.02 and 0.04 ± 0.01 µg/ml, respectively, while the GCF concentrations were 5.95 ± 0.85, 5.33 ± 1.12 and 4.98 ± 0.77 µg/ml, respectively. Mean GCF levels were significantly higher than mean serum levels at every point (P ≤ 0.02, paired t-test). Conclusion: The findings demonstrated that steady-state azithromycin concentrations in GCF were higher and more sustained than those in serum throughout the course of the study. Based on previous studies, the azithromycin concentrations found in GCF should inhibit A. actinomycetemcomitans, P. gingivalis and P. intermedia and also produce anti-inflammatory effects to modulate host responses. Both effects could be useful in the treatment of inflammatory periodontal diseases. Supported by grant DE018804.