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.

Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role.

The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-L-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-L-arginine assay, (2) significant inhibition of lambda-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.

Roxithromycin penetration into gingiva and alveolar bone of odontoiatric patients.

The concentrations of the new macrolide antibiotic roxithromycin in plasma, saliva, gingiva, and alveolar bone were studied in 24 odontoiatric patients treated with a first dose of 300 mg p.o. followed by three maintenance doses of 150 mg p.o., 12-hourly. Samples of blood, saliva, gingiva, and bone were collected at various time points up to 24 h after the last dosing, and the roxithromycin concentration was measured microbiologically, using Bacillus subtilis ATCC 6633 as the reference organism. Pharmacokinetic analysis was performed according to a two-compartment open model with first-order absorption. The plasma, gingiva, and alveolar bone peak concentrations were 6.12 +/- 1.94 mg/l, 6.55 +/- 2.54 mg/kg, and 5.09 +/- 1.60 mg/kg, respectively. Low levels of roxithromycin were detected in saliva (0.67 +/- 0.12 mg/l at the 3rd h). The values of the area under the concentration-time curve for plasma, gingiva, and bone were 59.47 mg/l.h, 51.88 mg/kg.h and 46.80 mg/kg.h, respectively; the half-life values were 7.52 h for plasma and 6.36 and 5.20 h for gingiva and bone, respectively. These results indicate that roxithromycin reaches high levels in periodontal tissues.