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

从生理生化机制出发，利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通过大鼠肠管和Caco-2细胞评价并促进药物的肠道吸收。为了阐明药物的吸收机理，促进药物的吸收，M.Hashida提出了一种新的技术。A.Tsuji阐明了药物通过细胞膜转运的机制，并成功地开发了调控机制。K.Inui利用培养的尿表皮细胞对小管药物分泌机制进行了精确分析。S.Awazu阐明了药物毒性作用出现的分子机制。J.Watanabe和N.Yata分别成功预测了大分子化合物和基础药物的组织分布。t.t arasaki根据病毒在组织中的受体分布和DNA拓扑异构酶I和DNA拓扑异构酶ii等抗癌药物的细胞杀伤动力学，分析并阐明了病毒在组织中的转运。S.Higuchi利用种群动力学模型开发了个体化给药。sugiyama成功地调控了受体介导的生物活性大分子清除。M.Hanano对整个研究进行了概括，分析了镇痛药的药代动力学与作用的关系，以期建立基于药物有效性及其毒性所涉及的生理生化机制的药代动力学。这些重要的成果于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提出。

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.