Kikuchi Junko, Yamazaki Koichi, Kikuchi Eiki, Ishizaka Akitoshi, Nishimura Masaharu
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Clin Ther. 2007 Jan;29(1):123-30. doi: 10.1016/j.clinthera.2007.01.005.
Bronchoalveolar lavage (BAL) is an established technique for measuring antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar and alveolar regions; however, the results may not reflect concentrations in bronchial regions. Bronchoscopic microsampling (BMS) is a technique that makes it possible to obtain multiple samples from bronchial ELF.
BMS and BAL were used to analyze the pharmacokinetics of gatifloxacin in bronchial ELF from healthy young adult subjects and adult patients with chronic bronchitis.
Bronchial ELF samples were obtained by BMS at 1, 2, 3, 4, 6, 10, and 24 hours after administration of a single oral dose of gatifloxacin 200 mg in healthy young adult (aged 20-25 years) subjects, and at 1, 2, 4, and 10 hours after a single dose in patients with chronic bronchitis (aged > or =20 years). At least 1 month after the initial BMS, alveolar (BAL) and bronchial (BMS) ELF samples were obtained from another group of healthy subjects 2 hours after administration of a single oral dose of gatifloxacin 200 mg for comparison of gatifloxacin concentrations in samples obtained by the 2 techniques.
Bronchial ELF samples were obtained from 8 healthy subjects and 5 patients with chronic bronchitis; alveolar ELF samples were obtained from a separate group of 5 healthy subjects. For the healthy subjects, the mean (SD) AUC(0-24) in serum and bronchial ELF, corrected for mg/kg doses, was 4.6 (1.1) and 7.6 (3.5) mg x h/L, respectively. In the patients with chronic bronchitis, the AUC(0-10) in serum and bronchial ELF, corrected for mg/kg doses, was 3.9 (0.8) and 4.1 (1.5) mg x h/L. The C(max) in serum and bronchial ELF, corrected for mg/kg doses, was 0.6 (0.2) and 1.4 (0.8) mg/L in healthy subjects and 0.7 (0.2) and 0.7 (0.2) mg/L in patients with chronic bronchitis. In healthy subjects, the C(max) and AUC(0-24) were significantly higher in bronchial ELF than in serum (both, P < 0.05). Gatifloxacin concentrations were significantly lower in bronchial ELF obtained by BMS than in alveolar ELF obtained by BAL (P < 0.05).
Based on the findings of this study in small numbers of healthy young adult volunteers and patients with chronic bronchitis, BMS appears to be a promising method for measuring drug concentrations and determining the pharmacokinetic profile of gatifloxacin in bronchial ELF. Additional studies are needed to correlate measured concentrations obtained by BMS with clinical and/or microbiologic outcomes in larger populations.
支气管肺泡灌洗（BAL）是一种用于测量细支气管和肺泡区域上皮衬液（ELF）中抗生素浓度的成熟技术；然而，其结果可能无法反映支气管区域的浓度。支气管镜微量采样（BMS）是一种能够从支气管ELF获取多个样本的技术。
采用BMS和BAL分析加替沙星在健康年轻成年受试者和成年慢性支气管炎患者支气管ELF中的药代动力学。
在健康年轻成年（20 - 25岁）受试者单次口服200 mg加替沙星后1、2、3、4、6、10和24小时，以及慢性支气管炎患者（年龄≥20岁）单次给药后1、2、4和10小时，通过BMS获取支气管ELF样本。在首次BMS至少1个月后，从另一组健康受试者单次口服200 mg加替沙星2小时后获取肺泡（BAL）和支气管（BMS）ELF样本，以比较两种技术获取样本中加替沙星的浓度。
从8名健康受试者和5名慢性支气管炎患者获取了支气管ELF样本；从另一组5名健康受试者获取了肺泡ELF样本。对于健康受试者，血清和支气管ELF中经mg/kg剂量校正后的平均（标准差）AUC(0 - 24)分别为4.6（1.1）和7.6（3.5）mg·h/L。在慢性支气管炎患者中经mg/kg剂量校正后的血清和支气管ELF中AUC(0 - 10)分别为3.9（0.8）和4.1（1.5）mg·h/L。健康受试者血清和支气管ELF中经mg/kg剂量校正后的C(max)分别为0.6（0.2）和1.4（0.8）mg/L，慢性支气管炎患者中分别为0.7（0.2）和0.7（0.2）mg/L。在健康受试者中，支气管ELF中的C(max)和AUC(0 - 24)显著高于血清（均P < 0.05）。BMS获取的支气管ELF中加替沙星浓度显著低于BAL获取的肺泡ELF（P < 0.05）。
基于本研究在少量健康年轻成年志愿者和慢性支气管炎患者中的发现，BMS似乎是一种有前景的测量药物浓度和确定加替沙星在支气管ELF中药代动力学特征的方法。需要进一步研究将BMS测得的浓度与更大人群中的临床和/或微生物学结果相关联。
