Definition for Prodrug
From Biology Forums Dictionary
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, a process termed bioactivation. 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.
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 bioactivate 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 both chemical properties likely to improve absorption and the major metabolic pathways in the body is used to modify the structure of new chemical entities for improved bioavailability. Conversely, the creation of prodrugs is sometimes unintentional, for example with serendipitous drug discoveries, where the drug is only later identified as a prodrug after extensive drug metabolism studies.