Oral medications with hepatic metabolism are at higher risk for adverse events

Oral medications with significant hepatic metabolism are at higher risk for hepatic adverse events, finds this month's issue of Hepatology.

Reactive metabolites generated by hepatic metabolism are thought to play an important role in the pathogenesis of drug-induced liver injury, but supporting data are limited.

If this is true, then compounds with significant hepatic metabolism should cause more drug-induced liver injury than those without it.

Dr Craig Lammert and colleagues from Sweden examined the relationship between hepatic metabolism and drug-induced liver injury of prescription medications.

The research team systematically extracted the metabolism characteristics of 207 of the most widely prescribed oral medications in the United States.

Compounds with more than 50% hepatic metabolism were characterized

Hepatology

Hepatic adverse events of interest were alanine aminotransferase more than 3 times the upper limit of normal, jaundice, liver failure, liver transplantation, or fatal drug-induced liver injury.

Compared with compounds with lesser hepatic metabolism, compounds belonging to the significant hepatic metabolism group had significantly higher frequency of alanine aminotransferase more than 3 times the upper limit of normal liver failure and fatal drug-induced liver injury, but not jaundice or liver transplantation.

The team found that 12 compounds with no hepatic metabolism had no reports of liver failure, liver transplantation, or fatal drug-induced liver injury.

The research team examined the relationship between hepatic adverse events and combination of hepatic metabolism and daily dose.

Compounds with both significant hepatic metabolism and daily dose more than 50 mg were significantly more hepatotoxic than compounds belonging to other groups.

Compared with medications without biliary excretion, compounds with biliary excretion had significantly higher frequency of jaundice.

Dr Lammert's team concluded, ”Our study finds an important relationship between a compound's metabolism profile and reports of hepatic adverse events.”