Prodrug

A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug.^[1]^[2] Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug is absorbed, distributed, metabolized, and excreted (ADME).^[3]^[4]

Prodrugs are often designed to improve bioavailability when a drug itself is poorly absorbed from the gastrointestinal tract.^[2] A prodrug may be used to improve how selectively the drug interacts with cells or processes that are not its intended target. This reduces adverse or unintended effects of a drug, especially important in treatments like chemotherapy, which can have severe unintended and undesirable side effects.

IUPAC definition

Compound that undergoes biotransformation before exhibiting pharmacological effects.
Note 1: Modified from ref.^[5]
Note 2: Prodrugs can thus be viewed as drugs containing specialized nontoxic protective groups used in a transient manner to alter or to eliminate undesirable properties in the parent molecule.^[6]

^ Rautio J, Meanwell NA, Di L, Hageman MJ (August 2018). "The expanding role of prodrugs in contemporary drug design and development". Nature Reviews. Drug Discovery. 17 (8): 559–587. doi:10.1038/nrd.2018.46. PMID 29700501. S2CID 19489166.
^ ^a ^b Hacker M, Messer WS, Bachmann KA (2009). "Chapter 10.5: Elimination (Metabolism and Excretion)". Pharmacology: Principles and Practice. Academic Press. pp. 216–217. ISBN 978-0080919225.
^ Malhotra B, Gandelman K, Sachse R, Wood N, Michel MC (2009). "The design and development of fesoterodine as a prodrug of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine". Current Medicinal Chemistry. 16 (33): 4481–4489. doi:10.2174/092986709789712835. PMID 19835561.
^ Stella VJ, Charman WN, Naringrekar VH (May 1985). "Prodrugs. Do they have advantages in clinical practice?". Drugs. 29 (5): 455–473. doi:10.2165/00003495-198529050-00002. PMID 3891303. S2CID 195692168.
^ Wermuth CG, Ganellin CR, Lindberg P, Mitscher LA (1998). "Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998)". Pure and Applied Chemistry. 70 (5): 1129–1143. doi:10.1351/pac199870051129.
^ Vert M, Doi Y, Hellwich KH, Hess M, Hodge P, Kubisa P, Rinaudo M, Schué F (2012). "Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)" (PDF). Pure and Applied Chemistry. 84 (2): 377–410. doi:10.1351/PAC-REC-10-12-04. S2CID 98107080. Archived from the original (PDF) on 2015-03-19. Retrieved 2013-07-29.

[:0-1] Rautio J, Meanwell NA, Di L, Hageman MJ (August 2018). "The expanding role of prodrugs in contemporary drug design and development". Nature Reviews. Drug Discovery. 17 (8): 559–587. doi:10.1038/nrd.2018.46. PMID 29700501. S2CID 19489166.

[Hacker2-2] Hacker M, Messer WS, Bachmann KA (2009). "Chapter 10.5: Elimination (Metabolism and Excretion)". Pharmacology: Principles and Practice. Academic Press. pp. 216–217. ISBN 978-0080919225.

[3] Malhotra B, Gandelman K, Sachse R, Wood N, Michel MC (2009). "The design and development of fesoterodine as a prodrug of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of tolterodine". Current Medicinal Chemistry. 16 (33): 4481–4489. doi:10.2174/092986709789712835. PMID 19835561.

[4] Stella VJ, Charman WN, Naringrekar VH (May 1985). "Prodrugs. Do they have advantages in clinical practice?". Drugs. 29 (5): 455–473. doi:10.2165/00003495-198529050-00002. PMID 3891303. S2CID 195692168.

[IUPAC-5] Wermuth CG, Ganellin CR, Lindberg P, Mitscher LA (1998). "Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998)". Pure and Applied Chemistry. 70 (5): 1129–1143. doi:10.1351/pac199870051129.

[6] Vert M, Doi Y, Hellwich KH, Hess M, Hodge P, Kubisa P, Rinaudo M, Schué F (2012). "Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)" (PDF). Pure and Applied Chemistry. 84 (2): 377–410. doi:10.1351/PAC-REC-10-12-04. S2CID 98107080. Archived from the original (PDF) on 2015-03-19. Retrieved 2013-07-29.

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