Effects of variation in CYP2D6 metabolism with clinical response to two therapeutic agents

Based upon genetic make-up and the resultant ability to metabolize therapeutic agents, individuals can be classified as extensive (normal) metabolizers (EM), poor metabolizers (PM), or ultrarapid metabolizers (UM). Since codeine is metabolized into an active agent (morphine), poor metabolizers may require increased dosing for a given therapeutic effect, while ultrarapid metabolizers may build up excessive levels of morphine, leading to adverse sequelae. Conversely, nortriptyline is the active therapeutic agent and is metabolized to an inactive form. In this case, poor metabolism leads to adequate therapy but an increased incidence of side effects, while extensive metabolizers may require increased dosing for therapeutic effect.