Relationship between minimum therapeutic dose vs. ADE

Here at Affygility Solutions we often get asked, "Is there a relationship between the minimum therapeutic dose and the acceptable daily exposure value?"  The short answer is "NO."

In order to calculate an acceptable daily exposure (ADE)(also known as PDE) value for an active pharmaceutical ingredient, the entire set of available toxicology data must be critically reviewed. The minimum therapeutic dose is only one of the data points that is closely examined. Other important data points include genotoxicity, mechanism of action, length of studies, reproductive effects and much more.

As an example, the ADEs for oncology products may have relatively high minimum therapeutic doses, but have low ADEs. This is because when a patient has advanced stage cancer, the treating physicians are trying to "hit the tumor" with as much drug load as a patient can possibly tolerate. In this situation, severe adverse effects such as genotoxicity, reproductive effects, and a possible risk of cancer is allowed since you are trying to save a person's life.

However, an ADE is defined as "A dose that is unlikely to cause an adverse effect if an individual is exposed by any route at or below this dose every day for a lifetime" and is for the protection of the NEXT batch and any patient population. Many oncology products have reproductive effects at low doses or may be genotoxic. These severe low dose effects must be taken into consideration when determining the ADE.