INTRAPULMONARY PHARMACOKINETICS OF AZITHROMYCIN IN HEALTHY-VOLUNTEERSGIVEN 5 ORAL DOSES

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses, Bronchoscopy , bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 1 24, 172, 244, 340, and 508 h after the first dose was administered, Az ithromycin concentrations in epithelial lining fluid (ELF), alveolar m acrophages, peripheral blood monocytes, and serum were measured by hig h-performance liquid chromatography, Azithromycin was extensively conc entrated in cells and ELF, Drug concentrations in AMs (peak mean +/- s tandard deviation, 464 +/- 65 (mu g/ml) exceeded 80 mu g/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (pe ak, 124 +/- 28 mu g/ml) exceeded 20 mu g/ml up to 340 h (14 days), Azi thromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 mu g/ml ) and were detectable up to 172 h (7 days), when they were 20 times th e concurrent serum concentrations, Although the clinical significance of antibiotic concentrations in these compartments is unclear, the sus tained lung tissue penetration and extensive phagocytic accumulation d emonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellu lar or intracellular pulmonary infections.