Intrapulmonary pharmacokinetics of telithromycin, a new ketolide, in healthy Japanese volunteers.
The concentrations of telithromycin, a new ketolide antimicrobial agent, in alveolar macrophages (AMs) and bronchoalveolar epithelial lining fluid (ELF) were determined in order to investigate the transfer of the drug into target tissue, relative to plasma, following multiple oral doses of telithromycin. Twenty-four healthy male Japanese volunteers were randomly allocated to four groups. Each subject was given 600 or 800 mg of telithromycin once daily for 5 days, followed by bronchoalveolar lavage (BAL) 2 or 8 h after the last dose (group A and B: 600 mg, 2 and 8 h BAL time point; group C and D: 800 mg, 2 and 8 h BAL time point). The mean concentrations of the drug in AMs and ELF were 34.54 and 4.92 mg/liter in group A, 50.97 and 2.26 mg/liter in group B, 25.47 and 4.24 mg/liter in group C, and 108.22 and 4.31 mg/liter in group D, respectively, which markedly exceeded concentrations in plasma. These results demonstrated good transfer of telithromycin into AMs and ELF, suggesting good efficacy against common respiratory pathogens, including intracellular pathogens and atypical microorganisms.
Kadota
Jun-Ichi
J
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan. kadota@oita-med.ac.jp
Ishimatsu
Yuji
Y
Iwashita
Tetsuji
T
Matsubara
Yuichi
Y
Tomono
Kazunori
K
Tateno
Masao
M
Ishihara
Roza
R
Muller-Serieys
Claudette
C
Kohno
Shigeru
S
D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D006801:Humans; D048628:Ketolides; D008168:Lung / Q000378:metabolism*; D018942:Macrolides; D008297:Male; D011446:Prospective Studies
D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; C106791:telithromycin