ABSTRACT
Drug–drug interactions are thought to be responsible for between 7 and 22 per cent of adverse drug reactions and underlie about 9 per cent of revisions to safety-related label warnings. The detection and characterisation of drug–drug interactions is a major concern to companies involved in the discovery and development of new medicines, and the regulatory authorities which police the healthcare business. Drug–drug interactions can occur when two or more drugs administered simultaneously mutually interact in a manner which results in alteration of the pharma-cokinetic profile, pharmacological or toxicological response to one or both of the compounds. Drugs may interact via inhibition of absorption or elimination processes or induction of enzymes responsible for the metabolism of drugs. The consequences of such interactions may range from those of purely academic interest, such as minor changes in elimination or metabolite profiles, to overt toxicity or even fatal clinical outcomes. Drugs which interact with each other may cause loss or 270exaggeration of pharmacological effect, or confer an altered phenotype on the patient thus expanding the consequences of drug–drug interactions to apparently unrelated xenobiotic or endogenous metabolism. Interactions need not necessarily be confined to the effects of one drug on another: drugs may affect endogenous metabolic processes (e.g. 6β-hydroxyation of cortisol increases with cytochrome P4503A4 induction); drugs may interact with ‘foodstuffs’ (e.g. furafylline inhibits caffeine clearance) or ‘foodstuffs’ which contain potent pharmacological principles may interact with drugs (e.g. components of grapefruit juice can block terfenadine metabolism). The following discussion is essentially confined to drug–drug interactions.
