|
Drug Concentration and Effect |  |
| Drug therapy is intended to result in a particular pharmacologic response of desired intensity and duration while avoiding adverse drug reactions. The relationship between the administered dose and the clinical response has been investigated for some drugs using a pharmacokinetic/pharmacodynamic (PK / PD) modeling approach. However, a simpler relationship between the concentration of a drug and its effect in an idealized in vitro system is modeled mathematically to conceptualize
receptor occupancy and drug response. The model assumes that the drug interacts reversibly with its receptor and produces an effect proportional to the number of receptors occupied, up to a maximal effect when all receptors are occupied. The reaction scheme for the model is: The relationship between effect and the concentration of free drug for the model can be written: where E is the effect observed at concentration C, Emax is the maximal
response that can be produced by the drug, and EC50 is the concentration of drug that produces 50% of maximal effect. |
| The above equation describes a rectangular hyperbola. It is generally more convenient to plot dose-response data as the drug effect (ordinate) against log dose or concentration (abscissa). The transformation yields a sigmoidal curve that allows the potency of different drugs to be readily compared. In addition, the effect of drugs used at therapeutic concentrations commonly falls on the portion of the sigmoidal curve that is approximately linear, ie, between 20% and 80% of maximal
effect. This makes for easier interpretation of the plotted data. |
