Baldwin D R, Wise R, Andrews J M, Honeybourne D
Department of Thoracic Medicine, Dudley Road Hospital, Birmingham.
Thorax. 1992 Jul;47(7):504-7. doi: 10.1136/thx.47.7.504.
An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important.
Fifteen subjects undergoing fibreoptic bronchoscopy each had four bronchial biopsy samples taken. Thirty sections from 10 patients were examined and the proportion of tissue types noted, a morphometric analysis computer being used. The water distribution was investigated in the other biopsy specimens with radiolabelled markers.
There was pronounced variation in the relative proportions of tissue types. Ciliated epithelium occupied a mean of 22.3% of the biopsy sample, submucosa 53.4%, muscle 17.6%, and glandular tissue 7.0%. There were no differences between second and the fourth generation subcarinae and macroscopic normality of the mucosa was a good predictor of histological normality. The extracellular water content was 40% of the total weight of the specimen and the total water content was 70%.
These data provide the basis for pharmacokinetic study of drugs in bronchial mucosa. They show for pharmacokinetic study that macroscopically normal mucosa may be assumed to be histologically normal; that multiple biopsy specimens should be taken for any study, as there is considerable variation in the proportion of tissue types; that specimens from second and fourth generation subcarinae are the same; and that extracellular water contributes 40% to the total weight of the biopsy specimen.
研究肺部药物药代动力学的一种方法是测量支气管活检标本中的药物浓度。对该技术的主要批评在于支气管活检标本包含不止一种组织类型,且药物分布往往不均匀。因此,支气管活检标本的形态以及细胞外和细胞内间隙之间的水分分布很重要。
15名接受纤维支气管镜检查的受试者每人获取4份支气管活检样本。对来自10名患者的30个切片进行检查,并记录组织类型的比例,使用形态计量分析计算机。用放射性标记物在其他活检标本中研究水分分布。
组织类型的相对比例存在显著差异。纤毛上皮平均占活检样本的22.3%,黏膜下层占53.4%,肌肉占17.6%,腺组织占7.0%。第二代和第四代支气管分支之间没有差异,黏膜的宏观正常是组织学正常的良好预测指标。细胞外水分含量占标本总重量的40%,总水分含量为70%。
这些数据为支气管黏膜中药物的药代动力学研究提供了基础。它们表明,对于药代动力学研究,宏观正常的黏膜可被假定为组织学正常;由于组织类型比例存在相当大的差异,任何研究都应采集多个活检标本;第二代和第四代支气管分支的标本相同;细胞外水分占活检标本总重量的40%。