Drug Metabolism

Tam Nguyen
November 25, 2014
 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
 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
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.
Improve membrane permeability
 Improve absorption and distribution
 Improve solubility
 Alter metabolism
 Alter toxicity
 Alter elimination
 Carrier-linked
Simple prodrug that contains an active drug
linked with a carrier group that is removed
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
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
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
 Numerous catalytic esterases are present in
vivo to hydrolyze simple esters.
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.
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:
Drug Metabolism. (n.d.). Retrieved November 18, 2014, from
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