Interaction between piroxicam and azithromycin during distribution to human periodontal tissues

Non-steroidal anti-inflammatory drugs and antibiotics are important in the prevention of infections and pain associated with periodontal surgery as well as in the adjunctive therapy of periodontal disease. In this study, patients undergoing oral surgery were treated with piroxicam and azithromycin to examine the interactions of these drugs on periodontal tissues.

Sixty-six patients were assigned to 3 groups and treated for 3 days as follows: 1) piroxicam 20 mg/day; 2) azithromycin 500 mg/day; or 3) piroxicam 20 mg/day plus azithromycin 500 mg/day. Samples of blood, saliva, gingiva, and alveolar bone were collected during surgery and at days 0.5, 2.5, 4.5, and 6.5 after last dose. Piroxicam concentrations were assayed by high-performance liquid chromatography and azithromycin concentrations by microbiological assay.

In patients treated with piroxicam alone, the highest drug concentrations were found in plasma at each time point, but consistent piroxicam levels were also detected in gingival samples up to 4.5 days. The combined treatment with piroxicam plus azithromycin was associated with a reduction of piroxicam concentrations in periodontal tissues. In patients receiving azithromycin alone, high drug levels were measured in periodontal tissues up to 6.5 days. This distribution pattern did not vary in patients treated with piroxicam plus azithromycin.

Treatment with piroxicam or azithromycin alone ensures a favorable distribution of these drugs into periodontal tissues. However, upon combined administration, azithromycin interferes negatively with the periodontal disposition of piroxicam. This interaction might depend on the displacement of piroxicam from acceptor sites at the level of periodontal tissues.