Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid
Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid
复制标题
DOI：
10.1111/j.1440-1843.2007.01208.x
复制
发表时间：
2008-03-01
期刊：
影响因子：
6.9
通讯作者：
Nishimura, Masaharu
中科院分区：
文献类型：
--
作者：
Kikuchi, Eiki;Yamazaki, Koichi;Nishimura, Masaharu
背景和目的：BAL是一种用于测量细支气管肺泡区域上皮细胞衬里液（ELF）中抗生素浓度的既定技术。然而，结果可能无法反映支气管区域的浓度。支气管镜微量取样（BMS）是一种用于支气管ELF重复取样的技术。本研究的目的是确定的时间与浓度曲线的克拉霉素及其活性代谢产物，14-羟基-克拉霉素，在支气管ELF，由BMS.Methods测定：BMS进行后1，2，3，5和10小时单次口服200毫克克拉霉素在5名健康志愿者。结果：血清克拉霉素最大浓度（Cmax）为0.36 ± 0.07mg/L，支气管ELF为1.44 ± 0.49mg/L（P < 0.01）;血清中14-羟基-克拉霉素的Cmax为0.34 +/- 0.13 mg/L，支气管ELF中为0.68 +/- 0.34 mg/L。克拉霉素0 - 10 h的浓度-时间曲线下面积（AUC（0-10）），血清为2.10 +/- 0.49 mg.h/L，支气管ELF为7.37 +/- 2.07 mg.h/L（P < 0.01）。口服给药后3 h，肺泡ELF和AM中克拉霉素的浓度分别为4.84 +/- 3.39 mg/L和10.7 +/- 8.7 mg/L，分别为：单次口服克拉霉素可使支气管ELF中克拉霉素的C-max和AUC（0-10）显著高于血清，且肺泡ELF和AM中克拉霉素的浓度高于血清。BMS可用于测定克拉霉素在支气管ELF中的药代动力学特征。
Background and objective: BAL is an established technique for measuring antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar-alveolar regions. However, the results may not reflect concentrations in bronchial regions. Bronchoscopic microsampling (BMS) is a technique for repeated sampling of bronchial ELF. The objective of the present study was to determine the time versus concentration profile of clarithromycin and its active metabolite, 14-hydroxy-clarithromycin, in bronchial ELF, as determined by BMS.Methods: BMS was performed at 1, 2, 3, 5 and 10 h after a single oral administration of 200 mg clarithromycin in five healthy volunteers. BAL was performed 3 h after administration to determine clarithromycin concentrations in alveolar ELF and alveolar macrophages (AM).Results: The maximum concentration (C-max) of clarithromycin was 0.36 +/- 0.07 mg/L in serum and 1.44 +/- 0.49 mg/L in bronchial ELF (P < 0.01). C-max for 14-hydroxy-clarithromycin was 0.34 +/- 0.13 mg/L in serum and 0.68 +/- 0.34 mg/L in bronchial ELF. The area under the concentration-time curve from 0 to 10 h (AUC(0-10)) for clarithromycin was 2.10 +/- 0.49 mg.h/L for serum and 7.37 +/- 2.07 mg.h/L for bronchial ELF (P < 0.01). The concentrations of clarithromycin in alveolar ELF and AM, 3 h after oral administration, were 4.84 +/- 3.39 mg/L and 10.7 +/- 8.7 mg/L, respectively.Conclusions: A single oral dose of clarithromycin produces a significantly higher C-max and AUC(0-10) for clarithromycin in bronchial ELF than in serum, and higher concentrations in alveolar ELF and AM than in serum. BMS might be useful for measuring the pharmacokinetic profile of clarithromycin in bronchial ELF.