The therapeutic index (also known as therapeutic ratio), is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies). Quantitatively, it is the ratio given by the lethal or toxic dose divided by the therapeutic dose.
In animal studies, the therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50).
Lethality is not determined in human clinical trials; instead, the dose that produces toxicity in 50% of the population (TD50) is used to calculate the therapeutic index.
While the lethal dose is important to determine in animal studies, there are usually severe toxicities that occur at sublethal doses in humans, and these toxicities often limit the maximum dose of a drug.
Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. having little difference between toxic and therapeutic doses) include diazepam, digoxin, dimercaprol, theophylline, warfarin and lithium carbonate.
Therapeutic Index or ratio can be calculated using
= MND /MED
= LD50/ED50
Where: MND is Maximum Non Toxic
MED is Maximum Effective Dose L
LD50 = median lethal dose
ED50 = median effective dose
Drugs with narrow therapeutic window can be toxic at a little dose increase above the therapeutic dose. Some examples of drugs with a narrow therapeutic index are as follows:
- Warfarin
- Dimercapol
- tTheophylline
- Lithium
- Digoxin
- Phenytoin
- Gentamicin
- Amphoteracin B
- 5-fluouracil
- Zidovudine