Prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolized in vivo into an active drug within the body through metabolic process, such as hydrolysis of an ester form of the drug.

1. Mr. K. Naga Prashant,M . P h a r m , [ P h . D ] , FAG E ,
Associate Professor,
Narasaraopeta Institute Of Phar maceutical
Sciences

2. overview
 Introduction
 What is prodrug?
 Why use prodrugs?
 Classification of prodrugs
 Applications of prodrugs
 Esters
 Enalapril
 Conclusion
 References

3. Introduction
 Metabolism is an essential pharmacokinetic
process, which renders lipid soluble and non-
polar compounds to water soluble and polar
compounds so that they are excreted by various
processes.
 Drugs are considered xenobiotics and most are
extensively metabolized in humans.
 Not all drugs are bioavailable, in which this led to
the development of prodrugs.

5. Whatis Prodrug?
 Prodrug is a
pharmacological substance
administered in an inactive
form.
 Once administered, the
prodrug is metabolized in
vivo into an active drug
within the body through
metabolic process, such as
hydrolysis of an ester form
of the drug.

8. “Hard Drugs”
Compounds that contain structural
characteristics required for activity but are not
susceptible to metabolism
• Increased efficiency by avoiding metabolism
• No toxic metabolites are formed
• HOWEVER, less readily eliminated due to lack
of metabolism
“Soft Drugs”
These are the opposite of prodrugs. These
compounds are designed and synthesized as
ACTIVE compounds that readily undergo metabolic
inactivation to nontoxic products

9. Whyuse Prodrugs?
 Improve membrane permeability
 Improve absorption and distribution
 Improve solubility
 Alter metabolism
 Alter toxicity
 Alter elimination

10. ClassificationofProdrugs
 Carrier-linked prodrugs:
 Simple prodrug that contains an active drug linked with
a carrier group that is removed enzymatically.
 The carrier group must be non-toxic and biologically
inactive when detached from drug.
 Bioprecursors:
 A compound that is metabolized by molecular
modification into a new compound that may itself be
active or further metabolized to an active metabolite.

11. Applicationof Prodrugs
 Pharmaceutical applications
 Improvement of taste
 Improvement of odour
 Reduction of irritation
 Reduction of pain on injection
 Enhancement of drug solubility and dissolution rate
 Enhancement of chemical stability of drug
 Pharmacokinetic applications
 Enhancement of provability
 Prevention of pre-systemic metabolism
 Prolongation of duration of action
 Reduction of toxicity
 Site specific drug-delivery

13. Esters
 Esters are the most commonly employed prodrugs.
 Numerous catalytic esterases are present in-vivo to
hydrolyze simple esters.
Prodrug Active Form of Drug

14. Enalapril
 The mono ethyl ester of enalaprilat
 Enalaprilat was first discovered as an inhibitor of
angiotensin converting enzyme (ACE) and used to treat
hypertension.
 Due to its high polarity, note two COOH’s, it was not orally
bioavailable, and thus needed to be administered by
injection.

15. Enalapril-> Enalaprilat
http://www.drug3k.com/img4/enalapril_14733_9_(big)_.jpeg
http://www.benvenue.com/online_catalog/products/enalaprilat/
_jcr_content/par/text/image.123901685.image.png

18. Conclusion
 Prodrugs are inactive compounds which are converted to
active drugs in the body by the process of drug
metabolism.
 Prodrugs were designed to improve pharmacokinetic and
drug delivery properties.
 Esters are commonly used as prodrugs to make a drug less
polar and allowing it to cross cell membranes more easily.
 The nature of the ester can be altered to vary the rate of
hydrolysis.

19. References
 Alagarsamy, V. (2010). Textbook of medicinal chemistry (Vol. 1, pp. 71-79). New
Delhi: Reed/Elsevier.
 Testa, B., & Mayer, J. (2003). <i>Hydrolysis in drug and prodrug metabolism:
Chemistry, biochemistry, and enzymology</i>. Zürich: VHCA.
 Drug Metabolism. (n.d.). Retrieved November 18, 2014, from
http://www.merckmanuals.com/home/drugs/administration_and_kinetics_of_drugs
/drug_metabolism.html
 Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D., Järvinen, T., &
Savolainen, J. (n.d.). Prodrugs: Design and clinical applications. <i>Nature Reviews
Drug Discovery,</i> 255-270. Retrieved November 18, 2014, from
http://www.ncbi.nlm.nih.gov/pubmed/18219308
 Pharmacological Effects, Prodrugs (Definition, Examples) and Sources of Drug
Information. (n.d.). Retrieved November 18, 2014, from
http://epharmacology.hubpages.com/hub/Pharmacological-Effects-Prodrugs-
Definition-Examples-and-Sources-of-Drug-Information