Homma T, Min K Y, Yoneda S, Yoshida S, Nakagawa H
Gan To Kagaku Ryoho. 1983 Aug;10(8):1810-6.
A series of experiments with ACM was performed to evaluate the effect for local treatment of malignant pleurisy from the view points of (1) clinical response, (2) pharmacokinetics following intrapleural administration, and (3) pleural reaction. The results were as follows: (1) In 6 patients with malignant pleural effusion, ACM was intrapleurally administered at a dose of 40 mg. In 4 out of the 5 evaluable cases, an extreme decrease in the pleural fluid volume and suppression of reswelling were observed, including 2 cases found to be negative for tumor cells upon cytodiagnosis. (2) In 5 patients, the pharmacokinetics was studied by using compartment model. The clearance curves of ACM in pleural fluid were described by a two-compartment model. The mean half lives of initial phase and terminal phase were 0.78 hr, and 15.28 hr, respectively. The time to reach the maximal whole blood level was 1 to 2 hrs after pleural administration, followed by a slow decline. (3) The pleural reaction to ACM was studied in rabbits by scanning and transmission electron microscope. At a dose of 4 mg per kg of body weight, the shortened microvilli, the degenerated mesothelial cells and the disappearance of basement membrane were observed. On the basis of these findings, we suggest that ACM might be an agent of choice in the treatment of malignant pleurisy.
进行了一系列使用ACM的实验，从以下几个方面评估其对恶性胸膜炎局部治疗的效果：（1）临床反应；（2）胸腔内给药后的药代动力学；（3）胸膜反应。结果如下：（1）在6例恶性胸腔积液患者中，以40mg的剂量胸腔内注射ACM。在5例可评估病例中的4例中，观察到胸腔积液量极度减少且再膨胀受到抑制，其中2例经细胞诊断肿瘤细胞呈阴性。（2）在5例患者中，采用房室模型研究药代动力学。ACM在胸腔积液中的清除曲线用二房室模型描述。初始相和终末相的平均半衰期分别为0.78小时和15.28小时。胸腔给药后1至2小时达到全血最大水平，随后缓慢下降。（3）通过扫描电子显微镜和透射电子显微镜在兔子身上研究了ACM的胸膜反应。在每公斤体重4mg的剂量下，观察到微绒毛缩短、间皮细胞变性和基底膜消失。基于这些发现，我们认为ACM可能是治疗恶性胸膜炎的首选药物。
