Quantitative Prediction of Drug-Drug Interaction Caused by CYP Inhibition and Induction from <i>In Vivo</i> Data and Its Application in Daily Clinical Practices—Proposal for the Pharmacokinetic Interaction Significance Classification System (PISCS)

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  • Ohno Yoshiyuki
    Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo

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  • <i>In vivo</i>情報からのCYPの阻害及び誘導による薬物相互作用の定量的予測と臨床現場での応用—Pharmacokinetic Interaction Significance Classification System（PISCS）の提案
  • Symposium Review : In vivo情報からのCYPの阻害及び誘導による薬物相互作用の定量的予測と臨床現場での応用 : Pharmacokinetic Interaction Significance Classification System (PISCS)の提案
  • Symposium Review : In vivo ジョウホウ カラ ノ CYP ノ ソガイ オヨビ ユウドウ ニ ヨル ヤクブツ ソウゴ サヨウ ノ テイリョウテキ ヨソク ト リンショウ ゲンバ デ ノ オウヨウ : Pharmacokinetic Interaction Significance Classification System (PISCS)ノ テイアン

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Abstract

　Drug-drug interactions (DDIs) can affect the clearance of various drugs from the body; however, these effects are difficult to sufficiently evaluate in clinical studies. This article outlines our approach to improving methods for evaluating and providing drug information relative to the effects of DDIs. In a previous study, total exposure changes to many substrate drugs of CYP caused by the co-administration of inhibitor or inducer drugs were successfully predicted using in vivo data. There are two parameters for the prediction: the contribution ratio of the enzyme to oral clearance for substrates (CR), and either the inhibition ratio for inhibitors (IR) or the increase in clearance of substrates produced by induction (IC). To apply these predictions in daily pharmacotherapy, the clinical significance of any pharmacokinetic changes must be carefully evaluated. We constructed a pharmacokinetic interaction significance classification system (PISCS) in which the clinical significance of DDIs was considered in a systematic manner, according to pharmacokinetic changes. The PISCS suggests that many current ‘alert’ classifications are potentially inappropriate, especially for drug combinations in which pharmacokinetics have not yet been evaluated. It is expected that PISCS would contribute to constructing a reliable system to alert pharmacists, physicians and consumers of a broad range of pharmacokinetic DDIs in order to more safely manage daily clinical practices.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 138 (3), 337-345, 2018-03-01

    The Pharmaceutical Society of Japan

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