Prodrug

A prodrug is a metabolised in vivo into an active metabolite.

Rationale for Development

The rationale behind the use of a prodrug is generally for Absorption, Distribution, Metabolism, and Excretion (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 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 Psilocybin, also occur naturally.

Selected examples

• enalaprilat
• acyclovir
• dopamine
• intravenous prodrug of chloramphenicol, because pure chloramphenicol does not dissolve in water
• psilocin
• Heroin is deacetylated by esterase to the active morphine
• morphine, as well as several other compounds that may be active in analgesia
• nitric oxide
• Invega (paliperidone) is an atypical antipsychotic for schizophrenia. It's the active metabolite of risperidone (Risperdal).