DISTRIBUTION OF ORALLY-ADMINISTERED AZITHROMYCIN IN VARIOUS BLOOD COMPARTMENTS

The concentrations of azithromycin in whole blood, plasma, erythrocyte s and polymorphonuclear leucocytes (PMNLs) were measured in 6 healthy volunteers following the last administration of a three-day regimen of 500 mg once daily. Marked enrichment of azithromycin was observed in PMNLs; the drug concentration amounted to 119 +/- 31 (SD) mg/l 6 hours after the administration. Twelve days thereafter 42 +/- 10 mg/l azith romycin was still measured in the PMNLs, although the drug was no long er demonstrable in plasma (< 0.02 mg/l). The elimination of azithromyc in from the PMNLs (half-life 210 +/- 69 hours) was clearly slower than the elimination from plasma (half-life 93 +/- 70 hours). The maximal concentrations of azithromycin in plasma (0.64 +/- 0.27 mg/l) and eryt hrocytes (0.17 +/- 0.06 mg/l) were much lower and occurred earlier (t( max) = 3 hours) than those observed in the PMNLs. The enrichment facto r for azithromycin in PMNLs relative to plasma came to 177 +/- 92 at 3 hours or 1814 +/- 706 at 120 hours after the last administration. In a parallel in vitro study, the effect of accumulation of azithromycin in PMNLs on the intracellular survival of ingested staphylococci was i nvestigated. At subinhibitory extracellular concentrations of azithrom ycin as low as 0.03 mg/l (MIC = 1 mg/l), a significant reduction in ba cterial viability was observed, thus demonstrating antibacterial activ ity of the intracellularly enriched antibiotic.