Distribution of systemic ciprofloxacin and doxycycline to gingiva and gingival crevicular fluid

Background: Systemic fluoroquinolones and tetracyclines reach steady-state levels in gingival crevicular fluid (GCF) that are several-fold higher than their levels in serum. The mechanism by which this occurs is unclear, but gingival fibroblasts are known to accumulate these agents. Uptake by fibroblasts could enhance their distribution to gingiva. To test this hypothesis, steady-state levels of these agents were assayed in serum, gingival connective tissue (GCT), and GCF. Methods: Healthy subjects who needed resective periodontal surgery participated in the study. Approximately 78 hours prior to the surgical appointment, each subject began a 3-day regimen of ciprofloxacin or doxycycline. At the surgical appointment (scheduled approximately 6 hours after the last dose), samples of blood and GCT were collected. GCF samples were collected on paper strips and measured with an electronic device. Samples were extracted and analyzed by high performance liquid chromatography. Results: Mean ciprofloxacin levels in serum, GCT, and GCF were 0.40 mug/ml, 1.38 mug/g, and 1.66 mug/ml, respectively (P <0.001, N = 9). For doxycycline, these levels were 1.11 mug/ml, 2.03 mug/g, and 2.41 mug/ml, respectively (P = 0.002, N = 8). For both agents, the GCT and GCF levels were significantly higher than serum levels (P <0.05), but not significantly different from each other. Conclusions: Our findings suggest that fibroblasts could play an important role in the distribution of fluoroquinolones and tetracyclines to the gingiva. By accumulating these agents in GCT, fibroblasts could contribute to the relatively high levels they attain in GCF.