title: Intrapulmonary concentration of levofloxacin in patients with idiopathic pulmonary fibrosis.
abstract: Patients with idiopathic pulmonary fibrosis (IPF) have significantly impaired pulmonary diffusion, which may affect the pulmonary concentration of many drugs, including antibiotics. In this study, we compared the difference in pulmonary levofloxacin (LVFX) concentration between patients with normal lung function and IPF. The IPF group included 10 patients with a proven diagnosis of IPF and a diffusing capacity for carbon monoxide ranging from 40% to 70% of predicted values. The control group included 10 patients with normal pulmonary function. Blood and bronchoalveolar lavage fluid (BALF) were taken at 3-3.5 h after fasting. LVFX (500 mg) was administered orally. LVFX concentrations in the serum and BALF were determined using HPLC-MS/MC. The level of LVFX in alveolar epithelial lining fluid (ELF) was calculated using the following formula: LVFX ELF = LVFX BALF × (Urea serum/Urea BALF). No significant differences in age, body weight, height, and calculated creatinine clearance and BALF retrieval rate were observed between groups. LVFX serum concentrations in the IPF and control groups were (5.97 ± 1.28) μg/ml and (6.84 ± 3.43) μg/ml, respectively (P = 0.4727). ELF concentration of LVFX in the control group was (27.81 ± 21.36) μg/ml, while the concentration in the IPF group was (10.17 ± 2.46) μg/ml, less than half of that in the controls (P = 0.0058). The intrapulmonary concentration of LVFX in IPF patients was lower than those with normal lung function. Notably, however, the ELF LVFX concentration following 500 mg once-daily exceeded the MIC90 of common respiratory pathogens. Excellent antibacterial efficacy of LVFX can be expected for IPF patients in the treatment of respiratory tract infections.
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China.
authors.forename: Yanxun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China.
authors.forename: Chunguo
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Clinical Pharmacology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Lang
authors.affiliation: Department of Clinical Pharmacology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 100730 Beijing, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, #1 Shuaifuyuan Street, Dongcheng District, 100730 Beijing, China. Electronic address: xuzj@hotmail.com.
authors.forename: Zuojun
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D064704:Levofloxacin / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin
keywords: Alveolar epithelial lining fluid; Idiopathic pulmonary fibrosis; Levofloxacin; Pharmacokinetics