Division of Host Defense Sciences, Omics Health Sciences, Department of of Integrated Health Sciences, Nagoya University, Graduate School of Medicine, Tokai National Higher Education and Research System, 1-20 Daikou-minami 1-chome, Higashi-ku, Nagoya, 461-8673, Japan.
College of Bioscience and Biotechnology, Chubu University, 1200, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
J Breath Res. 2022 May 24;16(3). doi: 10.1088/1752-7163/ac6b4b.
It is important to know the drug level in the target tissue to determine its dose. Some methods rely on blood levels of a drug to estimate its concentration in the tissues, which can be inaccurate. We thought that drug levels in exhaled breath aerosol (EBA) to give a more accurate value of the level of a test drug in the lung. Rats were intravenously injected with the bronchodilator theophylline and exhaled breath was collected up to 10-20 min after administration. Immediately after breath collection, lung, liver, kidney, and blood were collected and the pharmacokinetics were examined using these samples. Awake free-moving rats were used to efficiently collect exhaled breath from rats with low tidal volume. The amount of exhaled breath of rats was estimated by the amount of exhaled water vapor, and the drug concentration in exhaled breath sample was expressed by the amount of water vapor as the denominator. By using the active sampling method in which the adsorbent is sucked by a pump, theophylline in rat exhaled breath could be measured accurately. When the correlation of theophylline concentration in each sample was examined, a high correlation (= 0.74) was found only in exhaled breath and lung tissue. EBA was considered better than blood in pharmacokinetic analysis of lung tissue.
了解目标组织中的药物水平对于确定剂量很重要。有些方法依赖于药物的血液水平来估计其在组织中的浓度，但这可能不准确。我们认为，呼气气溶胶（EBA）中的药物水平可以更准确地反映肺部测试药物的水平。大鼠静脉注射支气管扩张剂茶碱，给药后采集呼气 10-20 分钟。在收集呼气后立即采集肺、肝、肾和血液样本，并使用这些样本检查药代动力学。使用清醒自由移动的大鼠，可以有效地从潮气量低的大鼠中收集呼气。通过呼出的水蒸气量来估计大鼠呼出的气量，通过水蒸气量作为分母来表示呼气样本中的药物浓度。通过使用主动采样方法，即通过泵吸入吸附剂，可以准确测量大鼠呼气中的茶碱。当检查每个样本中茶碱浓度的相关性时，仅在呼气和肺组织中发现高度相关性（= 0.74）。EBA 被认为在肺组织的药代动力学分析中优于血液。
