Transcript The main objectives of produgs are as follow:

The main objectives of produgs are as
follow:
Improvement of lipophilicity
Enhancement of water solubility
Increased metabolic stability
Improvement of taste
site – specific drug delivery
prodrugs
• Prepared from a drug & a carrier site of
transporting the drug from the site of
application selectively to the target cells.
e.g.
Brain specific targeting of a hydrophilic drug
+
Lipophilic carrier (a dihydropyridine)
Result in a lipophilic prodrug
• Inside the brain
The lipophilic carrier is converted enzymatically
To a highly hydrophilic charged species which is
locked in the brain and then hydrolyzed back to
the drug and N-methyl nicotinic acid is eliminated
from the brain.
The dihydropyridine/pyridinium redox
chemical delivery system
CDS
XH group on the drug is an amine, hydroxyl
or carboxyl.
Lipophilic
prodrug
N-methyl nicotinic
acid
Interference with transport
characteristics
• The introduction of a hydrophilic disposable
moiety into the drug prevent its absorption
from the gastrointestinal tract.
e.g.
Decreased toxicity and adverse
reaction
• The presence of the thiol group in Captopril
is considered as one of the responsible factors
for the adverse reaction of these drugs.
• The masking of the SH group, which in vivo
regenerates this group, results in less toxic
and probably longer acting drug
.
Increased duration of action
• Bitolterol is a prodrug form of colterol in
which the catechol hydroxyl groups have
been converted to 4-methylbenzoic(p-toloyl) acid esters, providing
increased lipid solubility and prolonged
duration of action.
Bronchodilator Activity
• Furthermore, the prodrug is preferentially
distributed in lung tissues rather than the
plasma or heart so that the bronchodilator
effect, following subsequent
biotransformation of the prodrug, is not
associated with undesirable cardiovascular
effect, and is slow and prolonged.