Delayed enhancement of acetaminophen hepatotoxicity by general anesthesia using diethyl ether or halothane.

Acetaminophen (Tylenol) is a widely used analgesic/antipyretic drug which is enzymatically bioactivated, or toxified, by the cytochromes P-450 to a hepatotoxic reactive intermediary metabolite. Brief general anesthesia with diethyl ether has been shown to inhibit both the toxifying cytochromes P-450 and enzymatic glucuronidation, the latter constituting up to 60% of acetaminophen elimination via a nontoxifying pathway. Thus ether potentially could produce a temporally differentiated inhibition of bioactivating and "detoxifying" pathways, resulting in an enhancement of acetaminophen hepatotoxicity if the balance favored bioactivation.