Prodrugs

Prodrugs are inactive drug precursors that are enzymatically or chemically converted into active drugs within the body. They are mainly metabolized in the liver or at the site of action.

Compared to the active drug, most prodrugs have better absorption, better chemical stability, enhanced membrane permeability, no foul taste, and reduced adverse effects.

Usually, prodrugs contain an active drug covalently linked to a chemical group called a carrier. When a carrier-linked prodrug enters the body, enzymes metabolize the attached carrier, releasing the active drug.

For example, enalapril, an anti-hypertensive drug, is metabolized by liver esterase, producing enalaprilat. This active dicarboxylic acid otherwise requires IV administration.

In contrast, a bioprecursor prodrug is a chemically inert form of a drug without a carrier that is transformed enzymatically into an active drug in the body.

Levodopa, a bioprecursor for dopamine, is also an amino acid. It uses amino acid transporters to cross the blood-brain barrier, where decarboxylases cleave its carboxyl group to release the neurotransmitter.