A prodrug is a pharmacological substance (drug) administered in an inactive

(or significantly less active) form. Once administered, the prodrug

is metabolised in vivo into an active metabolite. The rationale behind the use
of a prodrug is generally for absorption, distribution, metabolism, and
excretion (ADME) optimization. Prodrugs are usually designed to improve
oral bioavailability, with poor absorption from the gastrointestinal
tract usually being the limiting factor.
Typ
e
Convertin
g site
Subty
pe
Tissue
location of
conversion
Examples
Typ
e I
Intracellul
ar
Type
IA
Therapeutic
target
tissues/cells
Acyclovir, 5-Flurouracil, Cyclophosphamide, Diethylstilbestrol
diphosphate,
L-Dopa, 6-Mercaptopurine, Mitomycine C, Zidovudine
Typ
e I
Intracellul
ar
Type
IB
Metabolic
tissues
(liver, GI
mucosal
cell,lung
etc)
Cabamazepine, Captopril, Carisoprodol, Heroin, Molsidomine,
Paliperidone,
Phenacetin, Primidone, Psilocybin, Suldinac, Tetrahydrofurfury
l disulfide
Typ
e II
Extracellu
lar
Type
IIA
GI fluids
Lisdexamfetamine, Loperamide
oxide, Oxyphenisatin, Sulfasalazine
Typ
e II
Extracellu
lar
Type
IIB
Systemic
circulation
and Other
Extracellular
Fluid
Compartme
nts
Acetylsalicylate, Bacampicillin, Bambuterol, Chloramphenicol
succinate,
Dihydropyridine pralixoxime, Dipivefrin, Fosphenytoin
Typ
e II
Extracellu
lar
Type
IIC
Therapeutic
Target
Tissues/Cell
s
ADEPTs, GDEPs, VDEPs
Adapted from Pharmaceuticals (2:77-81, 2009) and Toxicology (236:1-6, 2007).
[edit]Examples
Carisoprodol is metabolized into meprobamate. Carisoprodol is not a controlled substance in
the United States, but meprobamate is classified as a potentially addictive controlled
substance that can produce dangerous and painful withdrawal symptoms upon
discontinuation of the drug.
Enalapril is converted by esterase to the active enalaprilat.
Valacyclovir is converted by esterase to the active acyclovir.
Fosamprenavir is hydrolysed to the active amprenavir.
Levodopa is converted by DOPA decarboxylase to the active dopamine.
Chloramphenicol succinate ester is used as an intravenous prodrug of chloramphenicol,
because pure chloramphenicol does not dissolve in water.
Psilocybin is dephosphorylated to the active psilocin.
Heroin is deacetylated by esterase to the active morphine.
Codeine is demethylated by the liver enzyme CYP2D6 to the active morphine, as well as
several other compounds that may be active in analgesia.
Molsidomine is metabolized into SIN-1 which decomposes into the active compound nitric
oxide.
Paliperidone is an atypical antipsychotic for schizophrenia. It is the active metabolite
of risperidone.
Prednisone, a synthetic cortico-steroid drug, is converted by the liver into the active
drug prednisolone, which is also a steroid.
Primidone is metabolized by cytochrome P450 enzymes into phenobarbital, which is major,
and phenylethylmalonamide, which is minor.
Dipivefrine, given topically as an anti-glaucoma drug, is converted to epinephrine.
Lisdexamfetamine is metabolized in the small intestine to produce dextroamphetamine at a
controlled (slow) rate for the treatment of attention-deficit hyperactivity disorder
Diethylpropion is a diet pill that does not become active as a monoamine releaser or
reuptake inhibitor until it has been N-dealkylated to ethylpropion.
Fesoterodine is an antimuscarinic that is converted to tolterodine.
Tenofovir disoproxil fumarate is an anti-HIV drug (NtRTI class) that is converted
to tenofovir (PMPA).