Acetaminophen is the generic name in the United States for the N-acetylated derivative of p-aminophenol (paracetamol is the generic name used in Great Britain and several other countries). It is one of the most widely used analgesiclantipyretic agents in the world because of its overall efficacy and safety. In contrast to aspirin and nonsteroidal anti-inflammatory agents it does not cause gastrointestinal bleeding, and there is no association of its use with the development of Reye's syndrome. The major problem caused by acetaminophen is hepatotoxicity observed after large overdoses of the drug (see reviews by Hinson,'Prescott,'Black'). From 1976 to 1985, over 11,000 cases of suspected acetaminophen overdose were reported in the United States, most of these the result of intentional self-p~ isoning.~ Of 2540 of these patients who were treated with the antidote, N-acetylcysteine, only I 1 died. If N-acteylcysteine was administered within 16 hours after overdose, no deaths occurred.

The use of N-acetylcysteine as an antidote is based on an understanding of the mechanisms by which acetaminophen initiates hepatocellular damage. For the most part, these mechanisms were outlined by the pioneering studies of Mitchell et al.'-8 The studies demonstrated roles for several drug-metabolizing enzymes and cosubstrates in the formation of both detoxication and toxic products of acetaminophen. Because these enzymes and cosubstrates may be influenced by genetic and environmental factors, individuals may differ in their susceptibility to acetaminophen toxicity. In particular, alcoholics may be at increased risk.'