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Dose-Response Relationship

DOSE-RESPONSE RELATIONSHIP

The relationship between the dose (amount) of a drug and the response observed can often be extremely complex, depending on a variety of factors including the absorption, metabolism, and elimination of the drug; the site of action of the drug in the body; and the presence of other drugs or disease. In general, however, at relatively low doses, the response to a drug generally increases in direct proportion to increases in the dose. At higher doses of the drug, the amount of change in response to an increase in the dose gradually decreases until a dose is reached that produces no further increase in the observed response (i.e., a plateau). The relationship between the concentration of the drug and the observed effect can therefore be graphically represented as a hyperbolic curve (see Figure 1).

Often, however, the response (ordinate) is plotted against the logarithm of the drug concentration (abscissa) to transform the dose-response relationship into a sigmoidal curve. This transformation makes it easier to compare different dose-response curvessince the scale of the drug concentration axis is expanded at low concentrations where the effect is rapidly changing, while compressing the scale at higher doses where the effect is changing more slowly (see Figure 2).

Finally, there are two basic types of dose-response relationships. A graded dose-response curve plots the degree of a given response against the concentration of the drug as described above. The second type of dose-response curve is the quantal dose-effect curve. In this case, a given quantal effect is chosen (e.g., a certain degree of cough suppression), and the concentration of the drug is plotted against the percentage of a specific population in which the drug produces the effect. The median effective dose (ed50 or the dose at which 50% of the individuals exhibit the specified quantal effect) and the median lethal dose (ld50 or the dose at which death is produced in 50% of the experimental animals in preclinical studies) can be estimated from quantal dose-effect curves. With this type of curve, the relative effectiveness of various drugs for producing a desired or undesired effect, as well as the relative safety between various drugs, can be determined. The ratio of the LD50 to the ED50 for a given effect indicates the therapeutic index of a drug for that effect and suggests how selective the drug is in producing its desired effects. In clinical studies, the concentration of the drug required to produce toxic effects can be compared to the concentration required for a specific therapeutic effect in the population to estimate the clinical therapeutic index.

(See also: Drug Metabolism )

BIBLIOGRAPHY

Gilman, A. G., et al. (Eds.). (1990). Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon.

Nick E. Goeders

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