Establishment of a new theory for assessment of drug disposition

在化疗中，药物转运到疾病部位的功效是决定最终治疗成功的最重要因素之一。然而，有一些实验方法定量评估药物在器官中的处置，我们没有详细的信息，药物运输的病理条件下。本研究从器官灌流技术的发展和药动学分析理论的发展两个方向，尝试建立一种新的途径。在器官灌注技术方面，除常规的肝、肾灌注系统外，我们还建立了带或不带VX_2癌的兔股肌灌注和大鼠Walker 256肿瘤离体标本灌注的新实验方法。另一方面，基于统计矩分析的概念，推导出了药物局部分布的新分析方法。利用这些方法，我们已经评估了各种靶向系统，如亲脂性和大分子前药的组织转运，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.