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Dose response relationships modelled by dose response curves are used extensively in pharmacology and drug development. In particular, the shape of a drug's dose–response curve (quantified by EC50, nH and ymax parameters) reflects the biological activity and strength of the drug.
The EC 50 of a quantal dose response curve represents the concentration of a compound where 50% of the population exhibit a response, [5] after a specified exposure duration. For clarification, a graded dose response curve shows the graded effect of the drug (y axis) over the dose of the drug (x axis) in one or an average of subjects.
A trio of dose response curves. A distinction should be made between quantification of drugs binding to receptors and drugs producing responses. There may not necessarily be a linear relationship between the two values.
The IC 50 of a drug can be determined by constructing a dose-response curve and examining the effect of different concentrations of antagonist on reversing agonist activity. IC 50 values can be calculated for a given antagonist by determining the concentration needed to inhibit half of the maximum biological response of the agonist. [4]
Both of these parameters have sigmoidal dose–response curves. Thus, a favorable outcome in dose–response for tumor tissue is greater than that of normal tissue for the same dose, meaning that the treatment is effective on tumors and does not cause serious morbidity to normal tissue.
Threshold dose is a dose of drug barely adequate to produce a biological effect in an animal. In dose-response assessment, the term ‘threshold dose’ is refined into several terminologies, such as NOEL, NOAEL, and LOAEL. They define the limits of doses resulting in biological responses or toxic effects. [3]
Therapeutic (green) and side effect dose response curves (red) illustrating a typical starting and progressively increasing titrated doses (arrows). Drug titration is the process of adjusting the dose of a medication for the maximum benefit without adverse effects .
The dose ratio r is the ratio of the dose of agonist required for half maximal response with the antagonist present divided by the agonist required for half maximal response without antagonist ("control"). In other words, the ratio of the EC50s of the inhibited and un-inhibited curves. Thus, r represents both the strength of an antagonist and ...