A phase I determination of azithromycin in plasma during a 6-week period in normal volunteers after a standard dose of 500mg once daily for 3 days

Objectives: The pharmacokinetics of azithromycin were evaluated in 12 healthy volunteers. Methods: This was an open study in 12 healthy male subjects. Participants received a single dose of 2 x 250mg azithromycin (two azithromycin capsules) administered orally in the fasting state with 240ml water on three consecutive days. Results: After oral intake of two capsules of 250mg azithromycin over three consecutive days (the normal treatment regimen in adults), azithromycin was present in measurable levels in plasma (>5 mu g/L) for 7 to 17 days after the beginning of treatment. The apparent elimination half-life was very long (observed range: 49 to 108 hours, i.e. about 2 to 4.5 days). From the results in plasma, one can extrapolate that the azithromycin concentration would remain above 1 mu g/L (corresponding to concentrations in tissues above 0.1 mg/L) for up to 15 to 30 days following treatment. The elimination half-life of azithromycin (average of 76 hours) was in agreement with values of depletion rates in tissues corresponding to a half-life of 60 to 72 hours. Conclusion: In conclusion, the utility of the long exposure of patients with benign respiratory infections to azithromycin and to subinhibitory concentrations of azithromycin should be questioned.