3.29:
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.
3.29:
Prodrugs
Prodrugs are a class of pharmaceutical compounds that undergo a biotransformation process within the body to be converted into a pharmacologically active drug. Prodrugs are designed to improve the therapeutic properties of the parent drug, such as enhancing bioavailability, increasing stability, or reducing toxicity. The concept of prodrugs revolves around modifying the chemical structure of the original drug to make it more effective or convenient for administration.
Prodrugs help overcome limitations associated with the parent drug, such as poor solubility, limited permeability, or unfavorable pharmacokinetic properties. By chemically modifying the drug molecule to a prodrug, its absorption, distribution, metabolism, and elimination (ADME) characteristics can be enhanced, leading to improved therapeutic outcomes.
The activation of prodrugs typically occurs through various mechanisms, including enzymatic hydrolysis, oxidation, or reduction, which are inherent biological processes occurring mainly in the liver. In addition, some prodrugs are metabolized at the site of action, while others are transformed extracellularly in blood or gastrointestinal fluids.
Prodrugs offer several advantages in drug development. They can extend the life of a drug and can also enhance patient compliance by offering alternative routes of administration or reducing the frequency of dosing. They have been employed to target specific tissues or cells by utilizing site-specific enzymes or transporters, minimizing off-target effects. As a result, prodrugs offer improved drug efficacy, better safety, and patient convenience.