4/1/2023

Dr. apt. Yudi Wicaksono, S.Si., M.Si.

 Hampir semua obat memiliki sifat-sifat

fisikokimia dan biologis yang tidak diinginkan.
 Calon obat seringkali tidak dilanjutkan
pengembangannya karena masalah sifat
farmakokinetik rendah atau toksisitas tinggi
 Efek teraputik obat-obat tersebut dapat
ditingkatkan dengan menghilangkan sifat yang
tidak diinginkan dan mempertahankan sifat
yang diharapkan

→ dapat dilakukan melalui cara biologis, fisik atau

kimia.

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Prodrug
“Biologically inert derivatives of drug molecules that
undergo an enzymatic and/or chemical conversion in
vivo to release the pharmacologically active parent
drug.” (Adrien Albert, 1958)

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Prodrug Vs. Drug

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History of Prodrugs

PRODRUG CONCEPT

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 The drug–promoiety is the prodrug that is typically

pharmacologically inactive.

 The drug and promoiety are covalently linked via

bioreversible groups that are chemically or
enzymatically labile

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Limitation Of Prodrug:

Biotransformation (Metabolism)
of Drugs in the body

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Steps in Prodrug Design

 Identification of drug delivery problem

 Identification of desired physicochemical properties

 Selection of transport moiety which will give prodrug

desired transport properties be readily cleaved in the
desired biological compartment

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Classification of Prodrugs
 Based on therapeutic categories
 Based on the site of conversion
 Based on the structure

Classification based on therapeutic categories

 Anticancer prodrugs
 Antiviral prodrugs
 Antibacterial prodrugs
 Nonsteroidal anti-inflammatory
prodrugs
 Cardiovascular prodrugs

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Classification based on the site of conversion

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*ADEP/GDEP/VDEP = antibody-, gene- or virus-directed enzyme prodrugs

Classification based on the structure

A.Carrier linked prodrug (Bipartite,

Tripartite, and Mutual Prodrugs)

B. Bioprecursors

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A. Carrier linked prodrug

 Carrier linked prodrug consists of the attachment of a
carrier group to the active drug to alter its physicochemical
properties.

The subsequent enzymatic or non-enzymatic mechanism

releases the active drug moiety.

Carrier linked prodrug :

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A1. Bipartite prodrug

A.2 Tripartite prodrug

 The carrier group is attached via linker to
drug.

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A.3 Mutual prodrugs

 A mutual prodrug consists of two pharmacologically
active agents coupled together so that each acts as a
promoiety for the other agent and vice versa.
 A mutual prodrug is a bipartite or tripartite prodrug in
which the carrier is a synergistic drug with the drug to
which it is linked.
 Ex. : Benorylate is a mutual prodrug aspirin and
paracetamol.

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Mutual prodrug:

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B. Bioprecursors
 Bioprecursor prodrugs produce their effects after in
vivo chemical modification of their inactive form.
 Bioprecursor prodrugs rely on oxidative or reductive
activation reactions unlike the hydrolytic activation of
carrier-linked prodrugs.
 They metabolized into a new compound that may
itself be active or further metabolized to an active
metabolite.

Bioprecursors

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