| アブストラクト | Polypharmacy is common, and may modify mechanisms of drug-induced liver injury. We examined the effect of these drug-drug interactions on liver safety reports of four drugs highly associated with hepatotoxicity. In the WHO VigiBase, liver event reports were examined for acetaminophen, isoniazid, valproic acid, and amoxicillin/clavulanic acid. Then, we evaluated the liver event reporting frequency of these 4 drugs in the presence of co-reported medications. Each of the 4 primary drugs was reported as having more than 2000 liver events, and co-reported with more than 600 different medications. Overall, the effect of 2275 co-reported drugs (316 drug classes) on the reporting frequency was analyzed. Decreased liver event reporting frequency was associated with 245 drugs/122 drug classes, including anti-TNFalpha, opioids, and folic acid. Increased liver event reporting frequency was associated with 170 drugs/82 drug classes; in particular, halogenated hydrocarbons, carboxamides, and bile acid sequestrants. After adjusting for age, gender, and other co-reported drug classes, multiple co-reported drug classes were significantly associated with decreased/increased liver event reporting frequency in a drug-specific/unspecific manner. In conclusion, co-reported medications were associated with changes in the liver event reporting frequency of drugs commonly associated with hepatotoxicity, suggesting that comedications may modify drug hepatic safety. |
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| ジャーナル名 | Regulatory toxicology and pharmacology : RTP |
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| Pubmed追加日 | 2015/05/20 |
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| 投稿者 | Suzuki, Ayako; Yuen, Nancy A; Ilic, Katarina; Miller, Richard T; Reese, Melinda J; Brown, H Roger; Ambroso, Jeffrey I; Falls, J Gregory; Hunt, Christine M |
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| 組織名 | Gastroenterology, Central Arkansas Veterans Healthcare System and;Gastroenterology and Hepatology, Univ. of Arkansas for Med. Sciences, Little;Rock, AR, United States. Electronic address: asuzuki@uams.edu.;Clinical Safety, GlaxoSmithKline, Research Triangle Park, NC, United States.;Pharmacovigilance and Risk Management, Raptor Pharmaceuticals, CA, United States.;Safety Assessment, GlaxoSmithKline, Research Triangle Park, NC, United States.;Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park,;NC, United States.;Gastroenterology, Duke University Medical Center and Durham Veterans;Administration Medical Center, Durham, NC, United States. Electronic address:;Christine.Hunt@va.gov. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/25988394/ |
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