Tam Nguyen
November 25, 2014
CHEM4201
Introduction
 What is prodrug?
 Why use prodrugs?
 Classification of prodrugs
 Applications of prodrugs
 Esters
 Enalapril
 Conclusion
 References

Metabolism is an essential pharmacokinetic
process, which renders lipid soluble and nonpolar 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.

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.

http://s2.hubimg.com/u/7766331_f520.jpg
Improve membrane permeability
 Improve absorption and distribution
 Improve solubility
 Alter metabolism
 Alter toxicity
 Alter elimination

 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.
 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
 Esters
are the most commonly employed
prodrugs.
 Numerous catalytic esterases are present in
vivo to hydrolyze simple esters.
Prodrug
Active Form of Drug
The monoethyl ester of enalaprilat
 Enalaprilate 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.

https://www.medicinescomplete.com/mc/rem/2012/images/c10-fig-10-25.png
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
Prodrugs are inactive compounds which are
converted to active drugs in the body by the
process of drug metabolism.
 Prodrugs were design 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.

 Brochure

concept and application of prodrugs

Alagarsamy, V. (2010). Textbook of medicinal chemistry (Vol. 1, pp. 7179). 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_kine
tics_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-EffectsProdrugs-Definition-Examples-and-Sources-of-Drug-Information