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Gingival crevicular fluid concentrations of azithromycin in health and gingivitis

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2011, Master of Science, Ohio State University, Dentistry.
Azithromycin, a macrolide antibiotic is active against several periodontal pathogens, is taken up and concentrated inside gingival fibroblasts, oral epithelium and polymorphonuclear leucocytes. Interactions with host cells in gingiva could influence the pharmacokinetics of this agent in periodontal applications. This issue was examined in two separate clinical studies. The first study, described in Chapter 2, tested the hypothesis that steady-state concentrations of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum. Four healthy subjects 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 and on days 4 and 7. GCF samples were collected from maxillary posterior interproximal sites with paper strips. The strips were pooled and eluted with high purity water. After extraction with diethyl ether, 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 consistently higher than mean serum levels. 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 Minimum Inhibitory Concentration for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia. Azithromycin preferentially localizes in inflamed tissues, suggesting that its concentration in gingival crevicular fluid could be higher at gingivitis sites than in health. The study described in chapter 3 tested this hypothesis. Experimental gingivitis was induced in one maxillary posterior sextant in nine healthy subjects. Contralateral healthy sextants served as controls. Subjects took 500 mg of azithromycin followed by 250 mg 24 hours later. Four hours after the second dose, plaque was removed from the gingivitis sites. GCF was collected from 8 surfaces in both the gingivitis and control sextants and pooled separately. GCF samples were subsequently collected on days 1, 2, 3, 8 and 15 and their azithromycin content was determined with the bioassay procedure described in Chapter 2. On days 2 and 3, the pooled GCF volume at gingivitis sites was significantly higher than at control sites and the mean azithromycin content in 30 second GCF samples pooled from gingivitis sites was significantly higher than at control sites. However, there were no significant differences in GCF azithromycin concentration between the gingivitis and control pools at any point. Thus, the amount of azithromycin perfusing gingivitis sites is greater than at healthy sites, but its concentration in GCF is similar due to dilution by GCF. Thus the findings of the current pharmacokinetic studies provide a rationale for further clinical evaluation of the adjunctive benefits of azithromycin in the treatment of periodontitis
John Walters (Advisor)
Hua-Hong Chien (Committee Member)
Sarandeep Huja (Committee Member)
55 p.

Recommended Citations

Citations

  • Jain, N. (2011). Gingival crevicular fluid concentrations of azithromycin in health and gingivitis [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306783019

    APA Style (7th edition)

  • Jain, Nidhi. Gingival crevicular fluid concentrations of azithromycin in health and gingivitis. 2011. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1306783019.

    MLA Style (8th edition)

  • Jain, Nidhi. "Gingival crevicular fluid concentrations of azithromycin in health and gingivitis." Master's thesis, Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1306783019

    Chicago Manual of Style (17th edition)