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From the 13 January 1997 issue of Smart Drug News [v5n6]. Copyright (c) 1997. All rights reserved.

Dose-Response Curves and Therapeutic Index

Dose-response curves are routinely plotted for new compounds. These curves graph the concentration of a drug vs the degree of biological response. What is the lowest dose that causes a biological response? How fast does the biological response increase with increasing dose? At what dose is the biological effect maximal? The specific shape of the dose-response curve can be used to compare drugs to each other.

In this illustration, drug X and Y have similar dose-response curves, but drug X is more potent, achieving it’s 50% effect at 10^-6 M compared to 10^-5 M for drug Y (a 10-fold difference). And while drugs X and Z have similar potency, drug X is more efficacious, achieving 100% of the maximum biological effect, whereas drug Z only achieves 60%.

The Therapeutic Index

Another important statistic is the therapeutic index (TI), the ratio of maximum non-toxic dose (just below the minimal toxic dose) to the minimum effective dose. While TI is a good measure of overall safety, it does not necessarily predict clinical usefulness. For example, digoxin has an unfavorable TI, but is very useful clinically for treating heart conditions [Rang and Dale, 1987; Katzung and Berkowitz 1989]. ——GL