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Prodrug



A prodrug is a pharmacological substance (drug) which is administered in an inactive (or significantly less active) form. Once administered, the prodrug is metabolised in vivo into an active metabolite.

Additional recommended knowledge

Rationale for Development

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, often due to the chemical properties of the drug.

Additionally, the use of a prodrug strategy increases the selectivity of the drug for its intended target. An example of this can be seen in many chemotherapy treatments, in which the reduction of adverse effects is always of paramount importance. Drugs used to target hypoxic cancer cells, through the use of redox-activation, utilise the large quantities of reductase enzyme present in the hypoxic cell to convert the drug into its cytotoxic form, essentially activating it. As the prodrug has low cytotoxicity prior to this activation, there is a markedly lower chance of it "attacking" healthy, non-cancerous cells which reduces the side-effects associated with these chemotherapeutic agents.

In rational drug design, the knowledge of chemical properties likely to improve absorption and the major metabolic pathways in the body allows the modification of the structure of new chemical entities for improved bioavailability.

However, sometimes the use of a prodrug is unintentional, especially in the case of serendipitous drug discoveries, and the drug is only identified as a prodrug after extensive drug metabolism studies. Some prodrugs, such as Codeine and Psilocybin, also occur naturally.

Selected examples

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Prodrug". A list of authors is available in Wikipedia.
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