02.03.5 Prodrugs

Prodrugs are pharmacologically inactive drugs that have active metabolites.  They are designed so that the maximum amount of active drug reaches the relevant site of action to have the required pharmacodynamic effect.  An example of a prodrug is enalaprilat.  Enalaprilat is a potent inhibitor of angiotensin converting enzyme (ACE), and ACE inhibitors are commonly used in cardiovascular disease.  However, it would be pointless to administer enalaprilat orally, as it is not absorbed after oral administration.  To circumvent this, the pharmacological inactive prodrug enalapril is used.  Enalapril is absorbed and has an oral bioavailability of ~60%.  Enalapril is converted by esterases in the liver to enalaprilat, which is the beneficial ACE inhibitor.