Prodrugs

Prodrugs

A prodrug is formed by chemical modification of a biologically active drug that will liberate the active compound in vivo by enzymatic or hydrolytic cleavage. The objective of employing a prodrug is to increase drug absorp-tion and to reduce side effects. Therefore, a prodrug is often classified as a controlled release dosage form. Prodrugs which are more lipophilic than the parent drug can increase membrane penetration and thus drug absorp-tion. For example, phenytoin 2-monoglycerides, a lipophilic phenytoin prodrug, afforded significant increase in oral absorption and bioavailabil-ity. The prodrug form can protect the parent compound from hydrolysis or enzymatic attack. A series of ester prodrugs of proprandol protected the drug from first-pass metabolism. An example of a prodrug is enala-pril maleate, which on oral administration is bioactivated by hydrolysis to enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor used in the treatment of hypertension.