[New perspectives on paracetamol]

Paracetamol (acetaminophen) is well established as a leading non-prescription antipyretic analgesic drug. Future developments are likely to include new formulations to achieve rapid absorption for a fast onset of action, and prolonged absorption to extend the duration of action for regular long-term administration. Better dosage forms are also required for rectal administration. The availability of intravenous paracetamol has greatly extended the use of this drug as an adjunct to postoperative analgesia and for control of fever in the intensive care setting. Intravenous paracetamol is available in only a few countries at present, but it seems inevitable that it will be marketed much more widely in the future. The misuse of paracetamol as a fashionable agent for self-poisoning seems likely to continue, and liver failure may still occur in the small proportion of overdose patients who present too late for effective antidotal treatment with N-acetylcysteine. Much effort is being devoted to the study of the molecular mechanisms of paracetamol hepatotoxicity, and it is hoped that further advances may make it possible to prevent liver failure in all patients, irrespective of delays in presentation. At the same time, there is great interest in the mechanisms of the therapeutic actions of paracetamol and its effects on the different isoforms of cyclo-oxygenase. There will probably be important new findings in this area and these may lead to wider clinical use. Meantime, possible novel therapeutic applications for paracetamol include its use as an antioxidant to prevent atherosclerosis and cardiovascular disease by inhibiting the oxidation of low-density lipoproteins, and to prevent the formation of cataracts.