title: Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis.
abstract: We determined the concentration-time profiles of ciprofloxacin and amikacin in serum and alveolar epithelial lining fluid (ELF) of rats with or without pulmonary fibrosis and investigated the effect of pulmonary fibrosis on the capacity for penetration of antimicrobials into the ELF of rats. Pulmonary fibrosis was induced in rats with a single intratracheal instillation of bleomycin. After intravenous injection of ciprofloxacin or amikacin, blood and bronchoalveolar lavage fluid samples were collected. Urea concentrations in serum and lavage fluid were determined using an enzymatic assay. Ciprofloxacin and amikacin concentrations were determined by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. The mean ratio of ELF to plasma concentrations of ciprofloxacin at each time point in the normal group did not significantly differ from that in the pulmonary fibrosis group. However, the ratio of the ciprofloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) in ELF to the AUC0-24in plasma was 1.02 in the normal group and 0.76 in the pulmonary fibrosis group. The mean ELF-to-plasma concentration ratios of amikacin at each time point in the normal group were higher than those in the pulmonary fibrosis group, reaching a statistically significant difference at 1, 2, and 4 h. The ratio of the AUC0-24in ELF to the AUC0-24in plasma was 0.49 in the normal group and 0.27 in the pulmonary fibrosis group. In conclusion, pulmonary fibrosis can influence the penetration of antimicrobials into the ELF of rats and may have a marked effect on the penetration of amikacin than that of ciprofloxacin.
authors.affiliation: Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Ni
authors.affiliation: School of Pharmacy and Chemistry, Dali University, Yunnan, China.
authors.forename: Deqing
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hekun
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Bai
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, China chai301pharmacy@163.com liuyouningpla301@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Chai
authors.affiliation: Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, China.
authors.forename: Junchang
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, China chai301pharmacy@163.com liuyouningpla301@163.com.
authors.forename: Youning
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000583:Amikacin / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010539:Permeability; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents; D001761:Bleomycin; D002939:Ciprofloxacin; D000583:Amikacin
keywords: amikacin; ciprofloxacin; epithelial lining fluid; penetration; pulmonary fibrosis