INTRAPULMONARY PHARMACOKINETICS OF CLARITHROMYCIN AND OF ERYTHROMYCIN

The intrapulmonary pharmacokinetics of orally administered clarithromy cin (500 mg every 12 h for five doses) or erythromycin (250 mg every 6 h for nine doses) were studied in 32 healthy adult volunteers. Four o f the subjects, two in the clarithromycin group and two in the erythro mycin group, were smokers. Bronchoscopy, bronchoalveolar lavage, and v enipuncture were performed at 4, 8, 12, 24, and 48 h after administrat ion of the last dose of clarithromycin and at 4, 8, and 12 h after adm inistration of the last dose of erythromycin. Clarithromycin was measu red by high-performance liquid chromatography, and erythromycin was me asured by a microbiological assay. No systemic sedation was used. Ther e were no major adverse events. The concentrations of antibiotics in e pithelial lining fluid (ELF) were calculated by the urea dilution meth od. The volumes (mean +/- standard deviation) of ELF were 1.9 +/- 2.0 ml and 1.5 +/- 0.7 ml in the clarithromycin and erythromycin groups, r espectively (P > 0.05). There was no effect of smoking on the amount o f bronchoalveolar lavage fluid recovered, the volume of ELF, or the nu mber of erythrocytes present in the lavage fluid (P > 0.05 for all com parisons). The total number of alveolar cells, however, was almost thr eefold greater in the smokers versus that in the nonsmokers (P < 0.05) . Clarithromycin was concentrated in ELF (range, 72.1 +/- 73.0 mu g/ml at 8 h to 11.9 +/- 3.6 mu g/ml at 24 h) and alveolar cells (range, 50 5.8 +/- 293.1 mu g/ml at 4 h to 17.0 +/- 34.0 mu g/ml at 48 h), 14-(R) -Hydroxyclarithromycin was also present in these compartments, but at lower concentrations than the parent compound. The concentrations of e rythromycin in ELF and alveolar cells were low at 4, 8, and 12 h follo wing the last dose of drug (range, 0 to 0.8 +/- 0.1 mu g/ml in ELF and 0 to 0.8 +/- 1.3 mu g/ml in alveolar cells). The clinical significanc e of any antibiotic concentrations in these compartments is unclear, T he data suggest, and we conclude, that clarithromycin may be a useful drug in the treatment of pulmonary infections, particularly those caus ed by intracellular organisms.