Peroxisome proliferator-activated receptor alpha-mediated drug toxicity in the liver

Expert Opinion on Drug Metabolism & Toxicology
Maka S Hedrington, Stephen N Davis

Abstract

Drug-induced hepatic injury is the most common cause of acute liver failure in the United States. Peroxisome proliferator-activated receptor alpha (PPARα)-mediated drugs are included among the approximately 900 natural and synthetic substances, which have shown hepatotoxicity. Areas covered: This review will focus on fibrates - PPARα agonists and their implication in causing liver injury. Expert opinion: Compelling evidence for fibrate-induced hepatotoxicity is not available. Results have been varying because several large randomized clinical trials have reported similar elevations of plasma transaminase levels in fibrate or placebo treated groups. On the other hand, one meta-analysis has reported an increased risk of hepatotoxicity when fibrates are combined with statins. Fibrate induced clinically apparent liver damage has been demonstrated in case reports. However, there is a wide spectrum of clinical phenotypic presentations of these cases (onset of injury, pattern of enzyme elevation and resolution of the symptoms), which reduces the ability to identify specific cause and effect of any putative fibrate-induced hepatotoxicity. Thus, the current recommendations for using fibrates include monitoring of aminotransferase levels...Continue Reading

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Apr 9, 2019·ChemMedChem·Letizia GiampietroBarbara De Filippis
Sep 14, 2019·Journal of Clinical Pharmacy and Therapeutics·Shizhan MaHuihuan Sun
Oct 3, 2019·Current Opinion in Lipidology·Jean-Charles Fruchart, Raul D Santos
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Apr 10, 2021·Frontiers in Oncology·Yan TanPeng Wei

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