Prediction and control effectiveness and safety of a drug by means of pharmacokinetics based on physiological and biochemical mechanism of its disposition in body.

本文以生理生化机制为基础，运用药代动力学方法预测和控制药物在体内的处置，以提高药物的有效性和安全性。M.Hayashi利用大鼠小肠导管和Caco-2细胞评价和促进药物的肠吸收。桥田先生提出了一种新的技术，以阐明药物吸收的机制，并促进它。A.Tsuji阐明了药物通过细胞膜转运的机制，并成功地开发了调节。K.Inui利用培养的尿上皮细胞精确地分析了肾小管分泌药物的机制。S.Awazu阐明了药物毒性作用出现的分子机制。J.Watanabe和N.Yata分别成功地预测了大分子化合物和基本药物的组织分布。T.Terasaki根据DNA拓扑异构酶I和II等抗癌药物在组织中的受体分布和细胞杀伤动力学分析并阐明了病毒的组织转运。T.伊加成功地预测了组胺H_2受体拮抗剂的神经毒性卷积。S.Higuchi利用群体动力学模型发展了个体化给药。Y.Sugiyama成功地调节了受体介导的生物活性大分子的清除。M.Hanano对镇痛药的研究进行了总结，分析了镇痛药的药代动力学与作用的关系，旨在从镇痛药的药效和毒性所涉及的生理生化机制出发，发展镇痛药的药代动力学。1994年9月26日，在日本东京本乡东京大学安田厅举行的公开研讨会上发表了这些重要成果。

Our studies on predition and control of drug disposition in body for promoting the effectiveness and safety by means of pharmacokinetics based on physiological and biochemical mechanism are summarized as follows. M.Hayashi evaluated and promoted intestinal absorption of drugs by using rat intestinal duct and Caco-2 cell. M.Hashida presented a new technology in order to clarify mechanism of drug absorption and to promote it. A.Tsuji clarified mechanism of drug transport through cell membrane and developed the regulation successfully. K.Inui analyzed precisely mechanism of tubular secretion of drug by using cultured urinal epidermal cell. S.Awazu clarified molecular mechanism of appearance of drug toxic action. J.Watanabe and N.Yata succeeded prediction of tissue distribution in macro molecular compounds and in basic drugs, respectively. T.Terasaki analyzed and clarified transport into tissue of virus based on the receptor distribution in tissues and cell killing kinetics of anticancer drugs including DNA topoisomerase I and II.T.Iga succeeded prediction neurotoxic convolution by histamine H_2 receptor antagonists. S.Higuchi developed individualized dosing by using population kinetics model. Y.Sugiyama succeeded regulation of a receptor mediated clearance of biologically active macromolecule. M.Hanano generalized the whole studies and analyzed relationship between pharmacokinetics and action for analgesics in order to develop pharmacokinetics based on physiological and biochemical mechanism invoived by drug effective and its toxicity. These significant results were presented to open seminar held on September 26th in 1994 at Yasuda hall in the university of Tokyo, Hongo Tokyo Japan.