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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 toxic effects. Quantitatively, it is the ratio given by the toxic dose divided by the therapeutic dose. A commonly used measure of therapeutic index is the toxic dose of a drug for 50% of the population (TD50
LD50

In toxicology, the median lethal dose, LD50 , or LCt50 of a toxic substance or radiation is the Dose required to kill half the members of a tested population....
) divided by the minimum effective dose for 50% of the population (ED50).






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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 toxic effects. Quantitatively, it is the ratio given by the toxic dose divided by the therapeutic dose. A commonly used measure of therapeutic index is the toxic dose of a drug for 50% of the population (TD50
LD50

In toxicology, the median lethal dose, LD50 , or LCt50 of a toxic substance or radiation is the Dose required to kill half the members of a tested population....
) divided by the minimum effective dose for 50% of the population (ED50). A high therapeutic index is preferable to a low one: this corresponds to a situation in which one would have to take a much higher dose of a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect.

Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. with little difference between toxic and therapeutic doses) may have its dosage adjusted according to measurements of the actual blood levels achieved in the person taking it. This may be achieved through therapeutic drug monitoring
Therapeutic drug monitoring

Therapeutic drug monitoring is a branch of clinical chemistry that specializes in the measurement of medication levels in blood. Its main focus is on drugs with a narrow therapeutic range, i.e....
 (TDM) protocols. The therapeutic index for diazepam
Diazepam

Diazepam , first marketed as Valium by Hoffmann-La Roche, is a benzodiazepine derivative drug. It possesses anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant and amnestic properties....
 is somewhat forgiving, about = 100. Other drugs, however are much less so, such as Digoxin
Digoxin

Digoxin , also known as Digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin....
, which has an index of 2 or 3. Other examples of drugs with a narrow therapeutic range, that may require drug monitoring both to achieve therapeutic levels and minimize toxicity, include: dimercaprol
Dimercaprol

Dimercaprol or British anti-Lewisite , is a compound developed by British biochemists at Oxford University during World War II. It was developed secretly as an antidote for Lewisite, the now-obsolete arsenic-based chemical warfare agent....
, theophylline
Theophylline

Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names....
, warfarin
Warfarin

Warfarin is an anticoagulant. It was initially marketed as a pesticide against rats and mice, and is still popular for this purpose, although more potent poisons such as brodifacoum have since been developed....
 and lithium carbonate
Lithium carbonate

Lithium carbonate is a chemical compound with the chemical formula Li2CO3. This colorless salt is widely used in the processing of metal oxide and has received attention for its use in psychiatry....
. Some antibiotics require monitoring to balance efficacy with minimizing adverse effects, including: gentamicin
Gentamicin

Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacteriuml infections, particularly those caused by Gram-negative bacteria....
, vancomycin
Vancomycin

Vancomycin is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacterium. It has traditionally been reserved as a drug of last resort, used only after treatment with other antibiotics had failed, although the emergence of vancomycin-resistant organisms means that it is increasingly being...
, amphotericin B
Amphotericin B

Amphotericin B is a polyene antifungal medication, often used intravenously for systemic fungi infections. It was originally extracted from Streptomyces Streptomyces nodosus, a hypha bacterium, in 1955 at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the Orinoc...
, and polymyxin B
Polymyxin B

Polymyxin B is an antibiotic primarily used for resistant gram negative infections. Polymyxins bind to the cell membrane and alter its structure making it more permeable....
.

The effective therapeutic index can be affected by targeting
Targeted drug delivery

Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others....
, in which the therapeutic agent is concentrated in its area of effect. For example, in radiation therapy for cancerous tumors, shaping the radiation beam precisely to the profile of a tumor in the "beam's eye view" can increase the delivered dose without increasing toxic effects, though such shaping might not change the therapeutic index. Similarly, chemotherapy or radiotherapy with infused or injected agents can be made more efficacious by attaching the agent to an oncophilic substance, as is done in peptide receptor radionuclide therapy for neuroendocrine tumors
Neuroendocrine tumors

Neuroendocrine tumors, or more properly gastro-entero-pancreatic or gastroenteropancreatic neuroendocrine tumors , are cancers of the interface between the endocrine system and the nervous system....
 and in chemoembolization or radioactive microspheres therapy for liver tumors and metastases. This concentrates the agent in the targeted tissues and lowers its concentration in others, increasing efficacy and lowering toxicity.

See also

  • Effective dose
    Effective dose

    An effective dose in pharmacology is the amount of medication that produces a therapeutic response in 50% of the people taking it, sometimes also called ED-50....
  • IC50
    IC50

    The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. Often, the compound in question is a drug candidate....
  • LD50
    LD50

    In toxicology, the median lethal dose, LD50 , or LCt50 of a toxic substance or radiation is the Dose required to kill half the members of a tested population....
  • EC50
    EC50

    The term half maximal effective concentration refers to the concentration of a drug or antibody which induces a response halfway between the baseline and maximum....
  • Certain safety factor
    Certain safety factor

    The Certain Safety Factor is the ratio of the lethal dose to 1% of population to the effective dose to 99% of the population . This is a better safety index than the Median lethal dose for materials that have both desirable and undesirable effects, because it factors in the ends of the spectrum where doses may be necessary to produce a respon...