薬物動態·動力学の活用によるテーラーメード処方設計

支援システムの基盤技術の確立に関する研究

抄録

The pharmacokinetic and pharmacodynamic (PK/PD) approaches are essential for applying the large amount of knowledge that has been gained from recent pharmaceutical research in planning dosage regimens for individual patients in the clinical setting.However,processes for the application of such knowledge using these approaches have not yet been established and this has become a bottleneck in promoting personalized pharmacotherapy.
The aim of this study was to establish the fundamentals for a pharmacokinetics/pharmacodynamics-based computer-aided system for planning personalized dosage regimens.We first retrospectively applied PK/PD models based on receptor occupancy theory to 2 clinical cases to demonstrate the usefulness of this theory in preventing adverse drug reactions and dealing with any that occurred.Next,we developed PK models to explain time-dependent drug interactions,for instance reduced absorption of new-quinolones due to metal cations and decreased blood levels of cyclosporine due to induction of detoxifying proteins by St.John’s Wort.
In the personalization of dosage regimens for patients with renal dysfunction,we developed a procedure for obtaining a parameter for the contribution of renal excretion from the literature as well as a model to explain the pharmacokinetics of a combination containing a renally-excreted metabolic inhibitor.We also developed a procedure for standardizing information on pharmaceutical formulations in order to construct databases.
In conclusion,the present study provided procedures for use with computer-aided systems in estimating the time-profiles of concentrations,effects and adverse reactions of drugs based on their individual parameters and patient data,such as dosage regimen and physiological functions,as well as the fundamentals of computer-aided systems for planning personalized dosage regimens.All of this should help in achieving personalized pharmacotherapy.