Comprehensive study on the predition of drug disposition based on the physiological and anatomical mechanism.

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The aim of this study is to make a system which predict quantitatively the various alterations in the pharmacokinetics by expanding the study of physiological model recently developed for the analysis of drug disposition based on the physiological, anatomical, and biochemical mechanisms. This alterations in pharmacokinetics include the species difference, interindivisual difference, age difference, effect of circadian rhythm, pathological condition, drug-drug interaction, in addition, effect of chemical structure and character of pharmaceutical formulation. It is now a true objective to complete the system to predict these alterations comprehenssively. For example, a) to establish a general methodology in scaling-up the pharmacokinetics by making a data bank systematically, b) to make clear the mechanisms of drug disposition in pathological condition or in multiple dosage regiments and to complete the methodology of prediction and diagnosis by studying the mechanism of drug transport i … More n liver and kidney using cell or membrane vesicle system and by kinetic study using organ perfusion system, c) to predict the onset and offset of drug action by combining the studies on both drug-receptor interaction and pharmacokinetics. This group consisted of 13 members and continued the study for 2 years (1985 and 1986). This study has produced many original findings and important results. Special mention should be made on the following study: the analysis of pharmacokinetics of peptides based on the physiological transport mechanism, the prediction of the pharmacokinetics of antimicrobials based on the molecular mechanism and quantitative prediction of the pharmacological effect of these drugs, in addition, kinetic analysis of the process of transport and metabolism of drugs in kidney and liver based on physiological mechanism, especially, uneven distribution of the metabolic enzymes of conjugative ractions as well as oxidative reactions using isolated hepatocytes, and the establishement of the isolation of the baso lateral and brush border membrane vesicles from kidney and the kinetic analysis of active transport process using these membrane vesicle system. Meeting was held in every February in Tokyo and active discussions were made, which seemed to stimulate this project extremely. Less