The therapeutic ratio expresses the relationship between a medication’s effectiveness and its toxicity. It is also called the therapeutic index. Researchers determine this value in clinical trials and other studies by determining the dosage at which the medication becomes toxic, and dividing by the effective dosage. These studies rely on doses that perform that way in at least 50% of the study population. The higher the therapeutic ratio, the more of a medication a patient would need to take to develop toxic symptoms.
Care providers want to treat disease in patients while limiting side effects. The therapeutic ratio provides important information about how a medication performs in most patients, which a doctor can use to decide on the best course of treatment for a given patient. This can be especially important in the case of drugs with a Narrow Therapeutic Index (NTI), where the difference between a beneficial and toxic dose can be very slight.
A common example comes up in radiation therapy. This treatment is used for cancers and certain other conditions. The radiologist wants to kill the cancer cells and stop their growth, but must consider damage to the neighboring tissue in the process. Blasting a tumor with a very high dose of radiation could be dangerous for the patient. Instead, the radiologist considers the effective dose for the cancer, based on the type of tumor and location in the body, and takes care to avoid entering the danger zone where neighboring tissue would be destroyed.
Some toxicity may be considered an acceptable outcome with treatment because it may be necessary to resolve the problem. In radiation, for instance, it is impossible to treat a cancer without damaging some neighboring cells. Using the therapeutic ratio, care providers can determine the probability of toxicity in a patient’s case and weigh it against the benefits. In NTI drugs, it is also very important to calculate dosing correctly and warn patients. Taking two pills instead of one by accident, for example, could have serious consequences.
Lethality studies are not performed in human populations, for ethical reasons; killing patients in a clinical trial to find out how much medication constitutes a fatal dose would be frowned upon. Instead, researchers rely on toxicity reported in such studies, including side effects and serious complications. These can vary considerably depending on metabolism and other factors, which is why some patients experience serious complications at seemingly safe dosages, while others can overdose without long-term ill effects. The therapeutic ratio reflects the median range.
