Some drugs are given in an inactive form and must be converted by the body into the active compound. That inactive form is a prodrug. The strategy solves several problems. A prodrug can improve absorption, mask a bitter taste, reduce irritation, or target the drug to a specific tissue. Once inside the body, enzymes or chemical conditions convert it into the active drug.

Classic examples include codeine, which the liver converts to morphine, and enalapril, which becomes enalaprilat. Valacyclovir is a prodrug of acyclovir with much better oral bioavailability. Some prodrugs are designed to activate in specific conditions, such as low oxygen in tumors or high acidity in the stomach. This targeted activation can reduce side effects in healthy tissue. The conversion step adds a layer of control, but it also adds variability. Genetic differences in the enzymes that activate a prodrug can mean some patients get too little active drug and others get too much.

Why prodrugs are used:

• Improved absorption. Better passage through the gut wall.
• Reduced side effects. Less irritation at the site of administration.
• Targeted activation. Conversion in specific tissues or conditions.
• Better taste. Masking an unpleasant flavor.

Not every inactive compound is a prodrug. A prodrug is designed to be converted, usually by a predictable enzymatic pathway.