Accumulation of Ciprofloxacin and Minocycline by Cultured Human Gingival Fibroblasts

• Published in: Journal of dental research Vol. 81; no. 12; pp. 836 - 840
• Main Authors: Yang, Q., Nakkula, R.J., Walters, J.D.
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01.12.2002; SAGE PUBLICATIONS, INC
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - pharmacokinetics; Biological Transport, Active; Cells, Cultured; Ciprofloxacin - pharmacokinetics; Dentistry; Fibroblasts - metabolism; Gingiva - cytology; Gingiva - metabolism; Humans; Hydrogen-Ion Concentration; Minocycline - pharmacokinetics; Temperature; tetracycline; fluoroquinolone; antimicrobial chemotherapy; periodontitis
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910208101208

Through a mechanism that is unclear, systemic fluoroquinolones and tetracyclines can attain higher levels in gingival fluid than in blood. We hypothesized that gingival fibroblasts take up and accumulate these agents, thereby enhancing their redistribution to the gingiva. Using fluorescence to monitor transport activity, we characterized the accumulation of fluoroquinolones and tetracyclines in cultured human gingival fibroblast monolayers. Both were transported in a concentrative, temperature-dependent, and saturable manner. Fibroblasts transported ciprofloxacin and minocycline with Km values of 200 and 108 μg/mL, respectively, at maximum velocities of 4.62 and 14.2 ng/min/μg cell protein, respectively. For both agents, transport was most efficient at pH 7.2 and less efficient at pH 6.2 and 8.2. At steady state, the cellular/extracellular concentration ratio was > 8 for ciprofloxacin and > 60 for minocycline. Thus, gingival fibroblasts possess active transporters that could potentially contribute to the relatively high levels these agents attain in gingival fluid.