Clay Siegall discusses implications of widening the therapeutic window

All drugs have what’s known as a therapeutic window. This is the quantity of drugs that can be safely administered to the patient that will also be concentrated enough to have notable therapeutic effects. Ideally, the maximum effect should be sought for the drugs. However, getting the maximum desired effect often involves dosages that are unsafe for the majority of patients. This is the upper limit of the therapeutic window. It is the point beyond which more of the drug cannot safely be administered, due to dangerous accumulations in the bloodstream.

Many drugs that are commonly used to treat illnesses and symptoms in ambulatory patients have a very wide therapeutic window. Notable therapeutic effects of the drugs begin almost immediately, with small quantities of the drug being ingested or administered intravenously. The drug can also be safely given in a very wide range of quantities. This allows for the patient to have available a large reserve of therapeutic effects, should they be needed. Examples of drugs with a large therapeutic window are those such as non-steroidal anti-inflammatory drugs, statins, blood pressure medication and even cannabis, which may have, perhaps, the largest therapeutic window of any known drug today.

However, in the hospital setting, many of the drugs that are given to patients have a much narrower therapeutic window. These drugs are typically quite dangerous and cannot be administered without the close supervision of an attending physician or anesthesiologist. Examples of drugs with a very small therapeutic window are those such as Propofol, morphine and chemotherapeutic agents. What this means is that, should these drugs be given in even slightly excessive amounts, the risk of the patient overdosing and dying is extremely high.

This has long been a problem with all chemotherapeutic agents. The therapeutic window has been extremely narrow. Although chemotherapy is a highly effective form of cancer treatment, the amount that can be given to patients at one time is strictly limited by the highly toxic effects of the drug.

With antibody drug conjugates, Clay Siegall has devised a new form of chemotherapy, with a therapeutic window orders of magnitude wider than any class of chemotherapies that have come before.