Azithromycin concentrations in blood and gingival crevicular fluid after systemic administration

Azithromycin is a macrolide antibiotic that is active against several periodontal pathogens. Macrolides are taken up and concentrated inside gingival fibroblasts, which could influence their pharmacokinetics. This study tests the hypothesis that steady-state levels of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum.

Four healthy patients received an initial dose of 500-mg azithromycin followed by 250-mg doses on each of the next 2 days. Serum and GCF samples were obtained 2 hours after the last dose on day 2, and on days 4 and 7. GCF samples were collected from maxillary posterior sites with paper strips. The strips were pooled and eluted with high-purity water. After extraction, the azithromycin content of the serum samples and GCF eluates was determined with an agar diffusion bioassay.

On days 2, 4, and 7, the concentrations of azithromycin in blood serum were 0.22 ± 0.02, 0.08 ± 0.02, and 0.04 ± 0.01 μg/mL, respectively. The concentrations in GCF were 8.82 ± 1.25, 7.90 ± 1.72, and 7.38 ± 1.15 μg/mL, respectively. Mean GCF levels were significantly higher than mean serum levels (P ≤0.02; paired t test).

The findings demonstrate that the pharmacokinetic profiles of azithromycin are different in GCF and serum. At steady state, azithromycin concentrations in GCF were higher and more sustained than those in serum. Based on previous studies, the levels observed in GCF were above the minimal inhibitory concentration for Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Prevotella intermedia.