Homma T, Yoneda S, Komuro Y, Yoshida S, Min K Y, Takayama S
Gan To Kagaku Ryoho. 1983 Apr;10(4 Pt 2):1129-34.
Tetracycline has been used for the local treatment of malignant pleurisy ever since of Robinson (1972) reported its effectiveness. In this report, we try to elucidate possible mechanisms of action of this drug from the viewpoints of (1) pharmacokinetic analysis following intrapleural administration, and (2) pleural reaction. The results were as follows: (1) In 5 patients with malignant pleural effusion, 500 mg of doxycycline was injected into the pleural cavity and pharmacokinetic analysis was performed. The clearance curve of doxycycline in pleural fluid was described by either a one-compartment model or a two-compartment model. The mean half life of slow space was 33.3 hr, which suggested delayed excretion of this drug from pleural space. (2) The direct effect of doxycycline on pleura was studied in rabbits. At a dose of 10 mg per kg of body weight, the mesothelial cells became cuboid and contained vacuoles in their cytoplasma. With increasing dose up to 40 mg per kg, the changes in mesothelial cells were enhanced. In submesothelial tissue, edema and cellular infiltration were noticed. Three weeks later, normalization of mesothelium was observed, being followed by connective tissue proliferation. These findings may support the efficacy of tetracycline for local treatment of malignant pleurisy.
自罗宾逊（1972年）报道四环素对恶性胸膜炎的局部治疗有效以来，四环素一直被用于该疾病的治疗。在本报告中，我们试图从以下两个角度阐明该药物可能的作用机制：（1）胸腔内给药后的药代动力学分析；（2）胸膜反应。结果如下：（1）对5例恶性胸腔积液患者胸腔内注射500mg强力霉素，并进行药代动力学分析。胸腔积液中强力霉素的清除曲线可用一室模型或二室模型描述。慢室的平均半衰期为33.3小时，这表明该药物从胸腔内排泄延迟。（2）在兔子身上研究了强力霉素对胸膜的直接作用。当剂量为每公斤体重10mg时，间皮细胞变为立方形，细胞质中出现空泡。随着剂量增加至每公斤体重40mg，间皮细胞的变化加剧。在间皮下组织中，可见水肿和细胞浸润。三周后，观察到间皮恢复正常，随后出现结缔组织增生。这些发现可能支持四环素对恶性胸膜炎局部治疗的疗效。
