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

Abstract

The pharmacokinetics of azithromycin were evaluated in 12 healthy volunteers. 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. 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 microg/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 microg/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. 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.