Acetaminophen - Dose-dependent Drug Hepatotoxicity and Acute Liver Failure in Patients

摘要

BackgroundDrug-induced liver injury (DILI) is a rare but serious clinical problem. A number of drugs can cause severe liver injury and acute liver failure (ALF) at therapeutic doses in a very limited number of patients (<1:10,000). This idiosyncratic DILI (iDILI), which is currently not predictable in preclinical safety studies, appears to depend on individual susceptibility and the inability to adapt to the cellular stress caused by a particular drug. In striking contrast to iDILI, drugs with dose-dependent hepatotoxicity are mostly detected during preclinical studies and do not reach the market. One notable exception is acetaminophen (APAP, paracetamol), which is a safe drug at therapeutic doses but can cause severe liver injury and ALF after intentional and unintentional overdoses.