Scribd
Upload
123 views4 pages

Prodrugs: Uses and Examples

Prodrugs are inactive compounds that are metabolized in the body to an active drug. They are used to improve membrane permeability, prolong a drug's activity, mask toxicity and side effects, and vary a drug's water solubility. Common examples of prodrugs include levodopa, azathioprine, aspirin, esters of chloramphenicol, and hexamine. Prodrugs can improve drug delivery by increasing permeability, stability, solubility, or targeting specific sites.

Uploaded by

علي الطياري
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
123 views4 pages

Prodrugs: Uses and Examples

Prodrugs are inactive compounds that are metabolized in the body to an active drug. They are used to improve membrane permeability, prolong a drug's activity, mask toxicity and side effects, and vary a drug's water solubility. Common examples of prodrugs include levodopa, azathioprine, aspirin, esters of chloramphenicol, and hexamine. Prodrugs can improve drug delivery by increasing permeability, stability, solubility, or targeting specific sites.

Uploaded by

علي الطياري
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 4

Prodrugs

 Prodrugs are compounds which are inactive in vitro and converted in the body to active drug
usually by drug metabolism.
 Esters are commonly used as pro-drugs.

Uses:
• Improving membrane permeability
• Prolonging activity
• Masking toxicity and side effects
• Varying water solubility
• Drug targeting
• Improving chemical stability.
1- Prodrugs to improve membrane permeability
Example: Levodopa for dopamine
HO CH2 HO CH2
CO2H
CH2 C
H
NH2 NH2
HO HO
Dopamine Levodopa
-More polar but is an amino acid
• Useful in treating Parkinson’s Disease
-Carried across cell membranes by carrier proteins
• Too polar to cross cell membranes and BBB for amino acids
-Decarboxylated in cell to dopamine

2 Prodrugs to prolong activity


Example:
O2N
Azathioprine for 6-mercaptopurine
N

SH
S N

N Me
N N
N

N N N N
H H

6-Mercaptopurine Azathioprine
(suppresses immune response) Slow conversion to 6-mercaptopurine
• Short lifetime - eliminated too quickly Longer lifetime.

1
3 Prodrugs to mask toxicity and side effects
• Mask groups responsible for toxicity/side effects
• Used when groups are important for activity

Example: Aspirin for salicylic acid


O

OH
H3C O
CO2H
CO2H

- Salicylic acid Aspirin


• Analgesic, but causes stomach Phenol masked by ester
ulcers due to phenol group Hydrolysed in body

4 - Prodrugs to lower water solubility


• Used to reduce solubility of foul tasting orally active drugs
• Less soluble on tongue
• Less revolting taste
Example:
Palmitate ester of chloramphenicol (antibiotic)
OH Cl
H H
O O Cl N
H H Cl
N
Cl
O
OH
O Esterase OH
H H
O2N
Palmitate ester O2N Chloramphenicol

5- Prodrugs to increase water solubility


• Often used for i.v. drugs
• Allows higher concentration and smaller dose volume
• May decrease pain at site of injection
Example: Succinate ester of chloramphenicol (antibiotic)
HO O
Succinate ester
OH Cl
H H
N
O O Cl Cl
H H O
N Esterase
Cl OH
H
O
OH O2N
H 2 Chloramphenicol
O2N
6 -Prodrugs used to target drugs
N
Example: Hexamine
N
• Stable and inactive at pH>5 N
N
• Stable at blood pH
• Used for urinary infections where pH<5
• Degrades at pH<5 to form formaldehyde (antibacterial agent)

7 -Prodrugs to increase chemical stability

Example: Hetacillin for ampicillin

Ph O Ph O
Ampicillin
HN N CH3 H2N HN
S S CH3

H 3C CH3 CH3 CH3


N O N
O O
OH OH
Hetacillin O H3C CH3 O

3
Drug alliances
A sentry drug
 A sentry drug is a drug which is administered alongside another drug to
enhance the latter's activity.
1-Many sentry drugs protect their partner drug by inhibiting an enzyme which acts
on the latter (e.g. carbidopa and levodopa).

L-DOPA DOPAMINE
ENZYME

INHIBITION

HO NHNH2
C
Me CO2H

HO
CARBIDOPA

2-Sentry drugs have also been used to localize the site of action of local
anesthetics and to increase the absorption of drugs from the GIT
(e.g. adrenaline & procaine),
adrenaline constricts the blood vessels in the vicinity of the injection and so
prevents procaine being rapidly removed from the area by the blood supply.

HO
NH
HO CH3

Adrenalin
HO

You might also like