James G asked
Why is it important to determine the therapeutic index of drugs with known toxic effects?
Answer
The therapeutic index (TI) is an important concept to understand in regard to drug safety.
The therapeutic index essentially quantifies the safety of a drug (i.e. relates safety to a number). Therapeutic index is determined by the 'lethal dose' and the 'therapeutic dose' of a certain drug or pharmaceutical.
The therapeutic dose is the amount of a drug, that when taken, physiological benefits are seen. The lethal dose is the opposite and as the name implies, is the dose that when taken can lead to adverse physiological effects and fatal consequences.
More specifically, therapeutic index is often given as the following equation: LD50/TD50.
LD50 = Concentration of drug at which 50% of the population will have a lethal response to the drug
TD50 = Concentration of drug at which 50% of the population will have the desired therapeutic response
There are low therapeutic index drugs and high therapeutic drugs, represented by TI values of less than 1 to greater than 100. The lower the TI value, the greater the risk of a lethal dose of that drug. Drugs that have a low therapeutic index need to be used extremely carefully and more often than not, need concentration levels monitored when used.
To get a good idea of how therapeutic index works, we'll use the TI equation with two fictional drugs, Drug X and Drug Y.
Let's say the therapeutic dose of Drug X is 50 mg, and the lethal dose is 60 mg.
For Drug Y, the therapeutic dose is 50 mg, and the lethal dose is 800 mg.
Which drug is safer in terms of therapeutic index?
Drug X clearly has less room for error, with the therapeutic dose and lethal dose being relatively close together. The therapeutic index comes out to 1.2 (60 mg/50 mg).
For Drug Y, the therapeutic dose and lethal dose are much farther apart. The therapeutic index comes out to 16 (800 mg/50 mg).
According to the therapeutic index of Drug X and Drug Y, Drug Y is safer and has a larger window of safety.
As mentioned above, care needs to be taken when using drugs with a low therapeutic index due to the increased risk of adverse effects, especially if there is a dosing error or if there are peculiarities with how someone is metabolizing a drug. A good example of low therapeutic drugs are certain chemotherapy agents. They have a very narrow range of effectiveness when compared to the risk of adverse effects.
