Therapeutic index

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) 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 amount of a drug to do harm than the amount taken to do good.

$mbox\{Therapeutic\; ratio\}\; =\; frac\{mathrm\{TD\}\_\{50\{mathrm\{ED\}\_\{50$

Generally, a drug 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 (TDM) protocols. The therapeutic index for diazepam is somewhat forgiving, about = 100. Other drugs, however are much less so, such as Digoxin, which has an index of 2 or 3. [cite journal| journal=Anesth Prog.| year=2007 Spring| volume=54|issue=1|pages= 19–24
pmc= 1821133|title=Drug Therapy in Dental Practice: General Principles Part 2—Pharmacodynamic Considerations|first=Daniel E| last=Becker| doi=10.2344/0003-3006(2007)54 [19:DTIDPG] 2.0.CO;2| pmid=17352523] Other examples of drugs with a narrow therapeutic range, that may require drug monitoring both to achieve therapeutic levels and minimize toxicity, include: dimercaprol, theophylline, warfarin and lithium carbonate. Some antibiotics require monitoring to balance efficacy with minimizing adverse effects, including: gentamicin, vancomycin, amphotericin B, and polymyxin B.

An important related factor is the leverage of targeting. For example, shaping radiation beams 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, when chemotherapy or radiotherapy is infused or injected, the delivery ratio can be much higher when the chemotherapy agent or radioisotope is attached to an oncophilic substance — as is done in peptide receptor radionuclide therapy for neuroendocrine tumors and in chemoembolization or radioactive microspheres therapy for liver tumors and metastases — again, that might not change the therapeutic index.

See also

* Effective dose
* IC₅₀
* LD₅₀
* EC₅₀
* Certain safety factor

References