Paracetamol is the most widely used drug. It has mild analgesic (pain relieving) and antipyretic (fever reducing) properties. It is also known as acetaminophen and
-acetyl-p-aminophenol (APAP). It produces analgesic action by elevation of the pain threshold and antipyresis through action on the hypothalamic heat regulating center of the brain. Caffeine is an alkaloid which is a theophylline - like xanthine derivative. By intermolecular association with paracetamol, caffeine increases the solubility and transmembrane permeation of paracetamol. It enhances the pain relieving effects of paracetamol (Square Pharmaceuticals, 2012). It has also an intrinsic power to raise vessel tone in the cranial of the brain, which provides another benefit to treat migraine and headache. So it is often combined with paracetamol in over-the-counter and prescription analgesics (Frey, 2003). This combination is used to treat mild to moderate pain including headache, migraine, neuralgia, toothache and dysmenorrhoea pains. It is also used for symptomatic relief of sprains and strains, rheumatic pain, fibrosis, muscular aches and pains, influenza, feverishness and feverish colds (Square Pharmaceuticals, 2012). However, according to the Chemical Research in Toxicology study of USA it has been recently found out that this combination increases the risk of paracetamol toxicity (BBC News, 2007).
METABOLISM OF PARACETAMOL AND CAFFEINE IN THE BODY
Paracetamol is metabolized primarily in the liver, where its major metabolites include inactive sulfate and glucuronide conjugates, which are excreted by the kidneys. A minor metabolite is produced in minute amounts by cytochrome P450 isoenzymes in the liver and kidney. Cytochromes P450 2E1 (CYP2E1) and 3A4 (CYP3A4) convert paracetamol to a highly-reactive intermediate metabolite, N-acetyl-p-benzo-quinoneimine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione as shown in Figure 1.