Prodrugs

Prodrugs are inactive form of drugs, which are readily cleavable into active form of the drug under biological environment.

Fig. A pictorial representation of prodrug concept

A prodrug is designed to pass over barrier or barriers (For e.g., Gastro Intestinal Tract (GIT), Blood Brain Barriers (BBB)) utilizing through a chemical approach rather than a formulation approach. Therefore, it is an alternative to the redesign of the cleavable drug molecule. Prodrug concept mainly deals with three main objectives such as Pharmaceuticals, Pharmacokinetics and Pharmacodynamics.

Pharmaceutical benefits of prodrug

1. A prodrug approach actually enhance the bio availability of the parent drug by increasing its permeability through cell barriers.
2. Prodrug approach increases the solubility for poorly soluble drugs
3. Prodrug approach even it is also increases the stability of less stable drugs under biological condition
4. Prodrug can act as a drug vehicle to bring the drugs to specific areas of the body parts (target specific drug delivery)
5. Prodrug approach controls release dosage form of drug for short biological half-lives containing drugs (sustain release)
6. Prodrug approach enhance patient acceptance by enhancing pleasant taste or odor of active drug 
7. Prodrug approach reduce off target effects (decrease toxic effects) of an active drug 

Prodrugs classification

Prodrugs classified into two types based on carriers attached to the drug and drug derivatization. such as 

1) Carrier linked prodrugs: In which Pro linker covalently bound to the active drug but it readily cleaved by enzymes or non-enzymatically into parent active drug. These pro linkers are inactive, nontoxic and non-immunogenic.

Carrier linked prodrugs again sub divided into 2 types

a) Bipartite: In which one carrier directly attached to the drug

b) Tripartite: In which drug connected to linker through a spacer because in some cases drug directly connected to linker is unstable.

c) Mutual prodrugs: In which two drugs linked together using a linker

2) Bio precursors: In which no carrier or linker attached to a compound but normal compound readily metabolized under particular biological environment (cytochrome P450) to active drug.

Conclusion

Prodrugs can improve ADME properties i.e pharmacokinetics of drug molecule. The basic concept of prodrug approach is to maximize the bioavailability of active drug that reaches its site of action, the carrier of prodrug that will be removed by either enzymatic or chemical transformation. These bio cleavable prodrugs are target selective without losing effectiveness of parent drug.  

undoubtedly prodrugs playing major role in drug discovery and development process by overcoming pharmacokinetics properties. 

Further Reading

You can get more information regarding prodrugs from below given URL & PDFs link


1) Prodrugs: challenges and rewards URL link
2) Prodrug Design to Improve Pharmacokinetic and Drug Delivery Properties: Challenges to the Discovery Scientists URL link