Intracellular pharmacokinetics of telithromycin, a ketolide antibiotic, in alveolar macrophages.
OBJECTIVE
Telithromycin, a ketolide antibiotic, has an antibacterial range that covers intracellular parasitic pathogens that survive or multiply intracellularly in alveolar macrophages. The intracellular pharmacokinetics of TEL in alveolar macrophages was evaluated in vitro.


METHODS
Telithromycin (50 microm) was applied to NR8383 as cultured alveolar macrophages, followed by incubation at 37 degrees C or 4 degrees C. After incubation, the amount of telithromycin in cells was determined.


RESULTS
Telithromycin exhibited high accumulation in NR8383 and its intracellular accumulation was temperature dependent. Also, telithromycin distributed to the organelles and cytosol in NR8383 and, in particular, it accumulated in the acidic organelle compartments.


CONCLUSIONS
This study suggests that the high accumulation of telithromycin in NR8383 is due to its high influx via active transport systems and trapping in acidic organelles, such as lysosomes. Moreover, this study provides important information for optimizing the treatment of respiratory intracellular parasitic infections based on the intracellular pharmacokinetics of antibiotics and parasitic sites.
Togami
Kohei
K
Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Hokkaido, Japan.
Chono
Sumio
S
Seki
Toshinobu
T
Morimoto
Kazuhiro
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D048628:Ketolides / Q000493:pharmacokinetics*; D016676:Macrophages, Alveolar / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin