Permeability and concentration of levofloxacin in epithelial lining fluid in patients with lower respiratory tract infections.
The purpose of the study was to assess the bactericidal effects of a single oral dose of levofloxacin (LVFX) by examining the concentration of LVFX in alveolar epithelial lining fluid (ELF) from patients with lower respiratory tract infections (LRTI). Forty patients with LRTI took 500 mg of LVFX and then received a fiberoptic bronchoscopic procedure randomly 1, 4, 8, 12, or 24 hours following dosing. Bronchoalveolar lavage fluid and blood were collected at the time of the bronchopulmonary procedure, and the LVFX concentration was determined. The mean peak concentrations of LVFX in plasma and ELF were achieved at 1.5 hours (4.07 mg/L) and 1 hour (3.44 mg/L), respectively. The AUC(24h) samples were 50.12 mg . h/L and 34.51 mg . h/L, respectively. The permeability of LVFX, which was estimated based on the ratio of LVFX concentration in tissue fluids to that in plasma, was 0.78 on average across all time points. After a single dose of LVFX in patients with LRTI, the drug rapidly distributed into bronchopulmonary tissue, thereby suggesting this dose is capable of achieving the concentration in target organs required for bactericidal efficacy.
Zhang
Jing
J
Institute of Antibiotics, Huashan Hospital, No. 12 Wu-lu-mu-qi Middle Road, Shanghai 200040, China. zhangj61@yahoo.com
Xie
Xin
X
Zhou
Xin
X
Chen
Yu-Qing
YQ
Yu
Ji-Cheng
JC
Cao
Guo-Ying
GY
Wu
Xiao-Jie
XJ
Shi
Yao-Guo
YG
Zhang
Ying-Yuan
YY
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015242:Ofloxacin / Q000493:pharmacokinetics*; D011446:Prospective Studies; D020545:Respiratory Mucosa / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin