Interaction between piroxicam and azithromycin during distribution to human periodontal tissues.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases.

BACKGROUND: The recognition that periodontal diseases are associated with specific pathogens has led to interest in the use of antibacterial drugs for inhibition of these microorganisms. On these bases, the present study was aimed at evaluating the tissue distribution of the new macrolide antibiotic azithromycin in patients subjected to oral surgery for chronic inflammatory diseases of both marginal and periapical periodontium. METHODS: Thirty-two patients were treated with azithromycin 500 mg/day orally for 3 consecutive days, and drug concentrations in plasma, saliva, normal gingiva, and pathological periodontal tissues were evaluated. For this purpose, samples of blood, saliva, normal gingiva, granulation tissue, and radicular granuloma or cyst wall (from dentigerous cyst) were collected during oral surgery or 0.5, 2.5, 4.5, and 6.5 days after the end of pharmacological treatment; then, azithromycin levels were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the indicator organism. RESULTS: The concentrations of azithromycin in plasma, saliva, normal gingiva, and pathological tissues reached the highest values 12 hours after the last dose (0.37+/-0.05 mg/l, 2.12+/-0.30 mg/l, 6.30+/-0.68 mg/kg, and 11.60+/-1.50 mg/kg, respectively) and then declined gradually. Consistent levels of the drug in normal gingiva and pathological tissues could be detected, however, up to 6.5 days, indicating that azithromycin was retained in target tissues for a long time after the end of treatment. Moreover, azithromycin levels in both normal gingiva and pathological tissues exceeded the minimum inhibitory concentrations of most pathogens involved in the pathophysiology of chronic inflammatory periodontal diseases. Notably, azithromycin levels in pathological tissues were significantly higher than those in normal gingiva 0.5, 2.5, and 4.5 days after the last dose. CONCLUSIONS: The present results indicate a marked penetration of azithromycin into both normal and pathological periodontal tissues, suggesting that azithromycin represents a promising option in both adjunctive and prophylactic treatments of chronic inflammatory periodontal diseases.

Gastric mucosal distribution and clinical efficacy of azithromycin in patients with Helicobacter pylori related gastritis.

The gastric mucosal distribution of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients with duodenal ulcer and Helicobacter pylori-related gastritis. The time course of ulcer healing, H. pylori infection, and gastritis activity was also evaluated. Twenty patients (median age 50 years) received the following treatment for 1 month: three cycles of azithromycin (500 mg/day for 3 consecutive days) on days 1-3, 11-13 and 21-23 plus omeprazole (40 mg/day) for 30 consecutive days. Endoscopic biopsy specimens of gastric mucosa and blood samples were collected on days 0, 4, 7, 10, 20 and 30. An additional follow-up endoscopy was carried out on day 60. H. pylori infection was determined by both histology and rapid urease test. Azithromycin concentrations in both plasma and gastric mucosa were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the reference organism. Azithromycin concentrations in plasma ranged between 0.17 mg/L (95% CI: 0.08-0.26; n = 5) and 0.32 mg/L (95% CI: 0.21-0.43; n = 5) throughout the treatment period. In addition, azithromycin concentrations in gastric mucosa were significantly higher than plasma concentrations at all times examined and ranged from 18.5 mg/kg (95% CI: 15-20; n = 20) to 24.6 mg/kg (95% CI: 16.8-32.4; n = 5), Indicating that the drug was highly retained in the target tissue. Accordingly, the ratio of azithromycin mucosal level to plasma concentration varied between 77.9 (95% CI: 56.5-99.3; n = 5) and 112.7 (95% CI: 100.2-125.2; n = 5). At the end of treatment (day 30) H. pylori was no longer detected in 16 of 20 patients (80%), and this finding was consistent with a marked decrease in the grading of gastritis activity. At the follow-up endoscopy (day 60) the infection was eradicated in only four patients (20%). These data indicate a favourable distribution of azithromycin into gastric mucosa of patients with H. pylori infection and suggest that this new macrolide antibiotic represents a valuable option for treatment regimens against H. pylori. However, the low eradication rate achieved with azithromycin plus omeprazole is a source of concern and requires further investigation.

Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study.

Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed. Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate. While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori strains, respectively. These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H. pylori-associated diseases.

Periodontal tissue disposition of azithromycin.

The tissue penetration of azithromycin, the prototype of a new class of macrolide antibiotics named azalides, was studied in patients undergoing surgery for third-molar removal. Drug concentrations in plasma, saliva, and periodontal tissues were evaluated in 28 patients treated with azithromycin 500 mg/day per os for 3 consecutive days. Samples of blood, saliva, gingiva, and alveolar bone were collected during oral surgery, 12 hours, and 2.5, 4.5, and 6.5 days after the last dosing, and the azithromycin concentration was measured microbiologically by using Micrococcus luteus NCTC 8440 as the reference organism. The highest concentrations of azithromycin were observed 12 hours after the last dose in plasma, saliva, gingiva, and bone (0.33 +/- 0.04 mg/l, 2.14 +/- 0.30 mg/l, 6.47 +/- 0.57 mg/kg, and 1.86 +/- 0.15 mg/kg, respectively) and then declined gradually. However, consistent levels of the drug in saliva and periodontal tissues could be detected up to 6.5 days, indicating that azithromycin was retained in target tissues and fluids for a long time after the end of treatment. Among the samples examined, the highest concentration of azithromycin was found in the gingiva at each time studied. Moreover, the ratios of salivary or periodontal tissue levels versus plasma concentrations remained nearly unmodified from 12 hours up to 6.5 days. Overall, these results indicate a favorable disposition of azithromycin into saliva and periodontal tissues and suggest that this macrolide antibiotic represents a valuable option in the pharmacologic treatment of odontogenic infections.