The effect of metyrapone on the elimination kinetics and metabolic fate of acetaminophen in man

Acetaminophen is a commonly used analgesic and antipyretic which when taken in recommended doses is both safe and effective. However, acetaminophen ingested in large doses such as encountered in suicide attempts, may result in massive, sometimes fatal, hepatic and renal necrosis. Acetaminphen-induced hepatotoxicity results from the metabolic conversion of acetaminophen to a quantitatively minor reactive metabolite by cytochrome P-450-mediated oxidation. Direct inhibition of this role of metabolism may be useful in the treatment of acetaminophen overdose, possibly as an adjunct to N-acetylcysteine. To date, few clinical trials have been conducted to support the use of cytochrome P-450 inhibitors in this setting.