Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers

Owing to azithromycin's prolonged half-life, shorter and shorter dosage reg imens are being studied for treatment of respiratory tract infections. Prev ious studies have concluded that the 3 and 5 day (1.5 g total) regimens not only provide at least equal serum and WBC exposures but also equal efficac y rates. An earlier clinical study using the entire 1.5 g dose at once or t he current 3 day regimen in patients with atypical pneumonia noted equal ef ficacy. Similar trials are currently underway In both adult and paediatric populations. The goal of the present study was to investigate whether there were equal serum and WBC exposures when azithromycin was dosed as the curr ent 3 day regimen or as a single large dose. Equal exposures would help val idate future clinical trials of single dose regimens. Twelve healthy volunt eers received both azithromycin regimens (1.5 g single dose and 500 mg/day for 3 days) in random order. Serum and WBC samples were collected at baseli ne and repeatedly for 10 days following the first dose of each regimen. Ser um samples were assayed via HPLC (CV% < 10) and WBC samples via liquid chro matography/mass spectrometry (CV% < 10). Data were modelled using noncompar tmental methods. Statistics were via ANOVA with significance defined as P < 0.05. All subjects completed both regimens with minimal incidence of adver se effects. Serum data [mean (range)] demonstrated no significant differenc e in exposure between the two regimens [single 13.1 (3.02-20.6) mg<bullet>h /L versus 3 day 11.2 (2.98-24.5) mg .h/L: P = 0.12], although it favoured t he shorter regimen. WBC results demonstrated much higher exposures than see n with serum, but no significant difference between the two regimens was id entified. These results suggest that a single oral 1.5 g regimen of azithro mycin for respiratory tract infections should provide exposure at least equ al to currently approved treatment regimens.