Therapeutic index

The concept of therapeutic index refers to the relationship between toxic and therapeutic dose. This pharmacodynamic parameter is relevant to clinical practice because it determines how safe (or toxic) a drug is.

Article outline:

Therapeutic index equation

The therapeutic index of a drug is the ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response in a population of individuals.

Where: TD50 is the dose of drug that causes a toxic response in 50% of the population and ED50 is the dose of drug that is therapeutically effective in 50% of the population.

How therapeutic index is determined

Therapeutic index and quantal dose response curves

Both ED50 and TD50 are calculated from quantal dose response curves, which represent the frequency with which each dose of drug elicits the desired response or toxic effect in the population.

There are some important characteristics of quantal dose-response curves (see image above) that are worth noting:

  • Dose of drug in plasma is plotted in the horizontal axis while the percentage of individuals (animals or humans) that responds or shows a toxic effect is represented in the vertical axis.
  • These curves measure all or none (positive or negative) responses. Some examples of positive responses include: relief of headache for an antimigraine drug, increase in heart rate of at least 20 bpm for a cardiac stimulant, or 10 mmHg fall in diastolic blood pressure for an antihypertensive.
  • Data is obtained from a population. Unlike graded dose-response graphs, data for quantal dose-response curves is obtained from many individuals.

ED50

The graph below shows how ED50 is calculated.

The dose required to cause a therapeutic effect (positive response) in 50% of a population is the ED50.

TD50


The dose required to produce a toxic effect in 50% of the studied population is the TD50. For animal studies, LD50 is the dose that results in death of 50% of the population.

Narrow therapeutic index drugs

The list below mentions some examples of narrow therapeutic index drugs:

  • Warfarin
  • Lithium
  • Digoxin
  • Phenytoin
  • Gentamycin
  • Amphotericin B
  • 5-fluorouracil
  • AZT (zidovudine)

References and further reading

Craig, C. Modern Pharmacology With Clinical Applications. 6th ed. LWW, 2003

Golan, D. “Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy”. 2nd ed. LWW, 2008.

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