Final answer:
The route with the lowest rate of bioavailability is the oral route, as barriers within the gastrointestinal tract prevent full absorption into the bloodstream.
Step-by-step explanation:
The route with the lowest rate of bioavailability is the oral route due to the barriers present in the gastrointestinal tract, such as the acidic gastric environment, high levels of intestinal proteolytic activity, and the permeability barrier of the intestine. These barriers significantly reduce the fraction of the drug that is absorbed into the bloodstream. By comparison, parenteral routes like intravenous administration bypass these barriers and often result in higher plasma levels, indicating a higher bioavailability.
To illustrate, in the context of prodrugs and pharmaceutical development, it is often expressed that oral bioavailability can be limited. For example, valacyclovir achieves a significantly higher bioavailability when compared to its parent drug, acyclovir, due to the utilization of intestinal transporters that increase permeability and hence oral bioavailability.