著者

Hayato Akimoto Takuya Nagashima Kimino Minagawa Takashi Hayakawa Yasuo Takahashi Satoshi Asai

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.44, no.10, pp.1514-1523, 2021-10-01 (Released:2021-10-01)

参考文献数

57

被引用文献数

7

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Drug-induced liver injury (DILI) is a common adverse drug event. Spontaneous reporting systems such as the Japanese Adverse Event Report Database (JADER) have been used to evaluate the association between drugs and adverse drug events. However, the association of drugs with adverse drug events may be overestimated due to reporting biases. Therefore, it is important to objectively evaluate the association using liver function test values. The aim of the present study was to predict potential hepatotoxic drugs using real-world data including electronic medical records and the JADER database. A total of 70009 (2779 with DILI and 67230 without DILI) and 438515 (10235 with DILI and 428280 without DILI) Japanese adult patients were extracted from electronic medical records and the JADER database, respectively. Drugs with ≥100 DILI patients in both of the two databases were regarded as suspected drugs for DILI. We used multivariate logistic regression to evaluate the association between the suspected drugs and increased risk of DILI. Among the suspected drugs, broad-spectrum antibiotics such as meropenem, tazobactam/piperacillin and ceftriaxone were significantly associated with an increased risk of DILI, and meropenem had a greater risk of DILI in both of the two databases. Additionally, there were significant associations of mosapride and L-carbocisteine with increased risk of DILI. In addition to well-known associations between antibiotic drugs and DILI, mosapride and L-carbocisteine were found to be new potential signals of drugs causing hepatotoxicity. This study indicates potential hepatotoxic drugs that require further causality assessment.

著者

Mayu Hibi Sakura Sugiura Tomoyuki Nakagawa Takashi Hayakawa Masaya Shimada

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.70, no.5, pp.697-702, 2021 (Released:2021-05-01)

参考文献数

19

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We examined effects of a major lipotrope, myo-inositol, on the expression of primary glycolytic (glucokinase and phosphofructokinase) and fructolytic enzyme (ketohexokinase [KHK] and aldolase B) genes in the livers of rats fed a control diet, high-sucrose diet, or high-sucrose diet supplemented with 0.5% myo-inositol for 14 d. Supplementation with myo-inositol decreased the hepatic expression of fructolytic enzyme genes, but not that of glycolytic enzyme genes, and the levels of triglycerides, fatty acid synthase, and KHK proteins in high-sucrose diet-induced fatty liver. The study results suggest that myo-inositol represses primary fructlysis, but not glycolysis, in high-sucrose diet-induced fatty liver.