Establishment of a new theory for assessment of drug disposition

在化疗中，药物转运到病变部位的有效性是决定最终治疗成功的最重要因素之一。然而，有几种实验方法用于定量评估药物在器官中的处置，我们没有关于病理条件下药物转运的详细信息。在本研究中，我们试图从器官灌流技术和药代动力学分析理论的发展两个方向建立一种新的方法。在器官灌流技术方面，我们在常规肝肾灌流系统的基础上，建立了兔股肌伴或不伴VX_2肿瘤和大鼠Walker256瘤体外肿瘤灌流的实验方法。另一方面，我们基于统计矩分析的概念，推导出了一种新的药物局部处置分析方法。利用这些方法，我们评价了不同靶向系统的组织转运，如亲脂性和大分子前药，并阐明了它们的物理化学和生物学特性与靶向能力之间的关系。

In chemotherapy, an efficacy of drug transport to the disease site is one of the most important factors deciding final therapeutic success. However, there is a few experimental methodologies for quantative assessment of drug disposition in the organ and we have no detailed information about drug transport under the pathological condition. In this investigation, we have tried to establish a new approach from the two directions of developments of organ perfusion technique and pharmacokinetic analysis theory. Concerning the organ perfusion technique, we have established new experimental methods for perfusion of rabbit thigh muscle with or without VX_2carcinoma and isolated tumor preparation of rat Walker256 iumor in addition to ordinary perfusion systems of the liver and kidney. On the other hand, we have derived new analytical method for local disposition of drugs based on the statistical moment analysis concept. With these methods, we have evaluated tissue transport of various targeting systems such as lipophilic and macromolecular prodrugs and elucidated the relationships between their physicochemical and biological characteristics and targeting abilities.