Advancing Drug Interaction Management Based on the Pharmacokinetic Drug Interaction Significance Classification System (PISCS)

Abstract

I worked in a hospital pharmacy department, where I was responsible for managing drug safety information within the hospital, providing patient-specific drug information to physicians and other healthcare professionals, and offering medication guidance to patients. Through these responsibilities, I became keenly aware of the need to develop methodologies for predicting drug–drug interactions (DDIs) and to improve the communication of such information. To address these challenges, we have been working over the past 20 years on a pharmacokinetic drug interaction significance classification system (PISCS), designed for clinical use. We were the first to develop the PISCS as an alert system that can easily and comprehensively predict changes in drug clearance caused by cytochrome P450-mediated interactions on the basis of the contribution ratio of target metabolizing enzyme to the oral clearance of substrates (CR) and the inhibition ratio of inhibitors (IR) (the CR–IR method). Leveraging these research findings, I have actively promoted DDI management through academic conferences, committee work, lectures, and publications. Moreover, I have contributed to the development of guidelines based on PISCS concepts for evaluating DDIs and disseminating information related to drug development. Notably, in July 2018, the Ministry of Health, Labour and Welfare of Japan issued the Guideline on drug interaction for drug development and appropriate provision of information, which is currently internationally harmonized as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M12 guideline. Consequently, DDI evaluations in drug development are being conducted in accordance with this guideline, and the descriptions of DDIs in drug package inserts have been significantly improved.