SINGLE-DOSE INTRAPULMONARY PHARMACOKINETICS OF AZITHROMYCIN, CLARITHROMYCIN, CIPROFLOXACIN, AND CEFUROXIME IN VOLUNTEER SUBJECTS

The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, c iprofloxacin, and cefuroxime were studied in 68 volunteers who receive d single, oral doses of azithromycin (0.5 g), clarithromycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four sub jects each, the subjects underwent bronchoscopy and bronchoalveolar la vage at timed intervals following drug administration. Drug concentrat ions, including those of 14-hydroxyclarithromycin (14H), were determin ed in serum, bronchoalveolar lavage fluid, and alveolar cells (ACs) by high-pressure liquid chromatography. Concentrations in epithelial lin ing fluid (ELF) were calculated by the urea diffusion method. The maxi mum observed concentrations (mean +/- standard deviation) of azithromy cin, clarithromycin, 1411, ciprofloxacin, and cefuroxime in serum were 0.13 +/- 0.07, 1.0 +/- 0.6, 0.60 +/- 0.41, 0.95 +/- 0.32, and 1.1 +/- 0.3 mu g/ml, respectively (all at 6 h). None of the antibiotics excep t clarithromycin (39.6 +/- 41.1 mu g/ml) was detectable in ELF at the 6-h bronchoscopy. The movement into and persistence in cells was diffe rent for azithromycin and clarithromycin. In ACs azithromycin was not detectable at 6 h, reached its highest concentration at 120 h, and exh ibited the greatest area under the curve (7,403 mu g . hr ml(-1)). The peak concentration of clarithromycin (181 +/- 94.1 mu g/ml) was great er and occurred earlier (6 h), but the area under the curve (2,006 mu g . hr ml(-1)) was less than that observed for azithromycin. 14H was d etectable in ACs at 6 h (40.3 +/- 5.2 mu g/ml) and 12 h (32.8 +/- 57.2 mu g/ml). The peak concentration of ciprofloxacin occurred at 6 h (4. 3 +/- 5.2 mu g/ml), and the area under the curve was 35.0 mu g . hr ml (-1). The data indicate that after the administration of a single dose , azithromycin, clarithromycin, and ciprofloxacin penetrated into ACs in therapeutic concentrations and that only clarithromycin was present in ELF. The correlation of these kinetic observations with clinical e fficacy or toxicity was not investigated and is unclear, but the data provide a basis for further kinetic and clinical studies.