Recent advances in evaluation studies for drug-induced liver injury

Yokoi Tsuyoshi

doi:10.1254/fpj.20027

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Other Title

薬物性肝障害評価研究の進歩
創薬シリーズ(8)創薬研究の新潮流(41)薬物性肝障害評価研究の進歩
ソウヤクシリーズ(8)ソウヤクケンキュウノシンチョウリュウ(41)ヤクブツセイカンショウガイヒョウカケンキュウノシンポ

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Abstract

<p>With the recent progress in drug metabolism and pharmacokinetics studies, the attrition due to pharmacokinetics in clinical trials and post-marketing was reduced to less than 1%. On the other hand, attrition of clinical trials due to adverse effects and toxicity has remained high. In particular, drug-induced liver injury (DILI) is a major cause of discontinuation of clinical trials and withdrawal of drug candidates after marketing. DILI is roughly divided into intrinsic and idiosyncratic. The former is relatively easy to predict its onset in preclinical drug development, but the latter’s onset mechanism is still unknown and its onset prediction is difficult. We are investigating to develop an experimental animal model of idiosyncratic DILI (iDILI), clarify the pathogenic mechanism, and apply the obtained biomarker information to the establishment of an in vitro cell-based prediction test system. In this paper, we will introduce various animal models of iDILI, present status of pathogenic mechanism study, and classification of iDILI drugs, and introduce the recent progress of in vitro cell-based prediction test system and new causative factors of iDILI.</p>

Journal

Folia Pharmacologica Japonica

Folia Pharmacologica Japonica 155 (5), 323-328, 2020

The Japanese Pharmacological Society

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