Drug interactions - Metabolism

Many drugs rely on metabolism by different isoenzymes of cytochrome P450 (CYP) in the liver, especially 3A, 2D6, 2C9, 2C19, and 1A2. Interacting drugs have the potential to either increase the rate of metabolism by inducing the formation of more CYP isoenzyme or decrease metabolism by inhibiting isoenzyme activity. Enzyme inducers (e.g. phenytoin, rifampicin) generally reduce plasma concentrations although may enhance conversion of a pro-drug to its active form. Enzyme inhibitors (e.g. clarithromycin, cimetidine, grapefruit juice) have the opposite effect. Enzyme induction effects usually take at least a few days to manifest because of the need to synthesise new CYP enzyme. In contrast, the effects of enzyme inhibition may be rapid with the affected drug quickly reaching a new higher steady state concentration.