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Journal of Dental Research
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Biological

Accumulation of Non-steroidal Anti-inflammatory Drugs by Gingival Fibroblasts

M.M. Zavarella1, O. Gbemi2 and J.D. Walters1,*

1 Sections of Periodontology and
2 Oral Biology, College of Dentistry, The Ohio State University Health Sciences Center, 305 West 12th Avenue, P.O. Box 182357, Columbus, OH 43218-2357, USA

Correspondence: * corresponding author, walters.2{at}osu.edu

Non-steroidal anti-inflammatory drugs (NSAIDs) are used to manage pain and inflammatory disorders. We hypothesized that gingival fibroblasts actively accumulate NSAIDs and enhance their levels in gingival connective tissue. Using fluorescence to monitor NSAID transport, we demonstrated that cultured gingival fibroblasts transport naproxen in a saturable, temperature-dependent manner with a Km of 127 µg/mL and a Vmax of 1.42 ng/min/µg protein. At steady state, the intracellular/extracellular concentration ratio was 1.9 for naproxen and 7.2 for ibuprofen. Naproxen transport was most efficient at neutral pH and was significantly enhanced upon cell treatment with TNF-{alpha}. In humans, systemically administered naproxen attained steady-state levels of 61.9 µg/mL in blood and 9.4 µg/g in healthy gingival connective tissue, while ibuprofen attained levels of 2.3 µg/mL and 1.5 µg/g, respectively. Thus, gingival fibroblasts possess transporters for NSAIDs that are up-regulated by an inflammatory mediator, but there is no evidence that they contribute to elevated NSAID levels in healthy gingiva.

Key Words: naproxen • ibuprofen • analgesic • inflammatory periodontitis

Journal of Dental Research, Vol. 85, No. 5, 452-456 (2006)
DOI: 10.1177/154405910608500511
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