The therapeutic index of a drug is the ratio of the dose that exerts toxicity in 50% of the population (TD50) to the dose that exerts a therapeutic or effective response (ED50) in 50% of the population (TI=TD50 / ED50). Therapeutic index can also be derived from the ratio of the lethal, instead of toxic, dose in 50% of the population (LD50) that is measured in animal studies. The term represents the safety margin of a particular drug for clinical use, as high therapeutic index values indicate a wide margin between effective and toxic doses (fig).
In some cases, therapeutic index might not be a reliable indicator for quantifying drug risks and benefits as LD50 is primarily estimated from animal studies and doesn’t accurately depict the drug risks in clinical settings. In addition, therapeutic index doesn’t take into account the idiosyncratic responses in the population and, more importantly, the efficacy and the toxicity of a particular drug are subject to individual variations. Some of these variations can now be understood through pharmacogenomics.
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