title: Intracellular pharmacokinetics of telithromycin, a ketolide antibiotic, in alveolar macrophages.
abstract: 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.
authors: Department of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido Pharmaceutical University, Otaru, Hokkaido, Japan.
authors: Kohei
authors: K
authors: Togami
authors: Sumio
authors: S
authors: Chono
authors: Toshinobu
authors: T
authors: Seki
authors: Kazuhiro
authors: K
authors: Morimoto
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; C106791:telithromycin