chapter  13
38 Pages

Chapter Enzyme-Activated Prodrug Strategies for Targeted Drug Action

Prodrugs are bioreversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then produce its desired pharmacological effect.1-3 In most cases, prodrugs are simple chemical derivatives that are one or two chemical or enzymatic steps away from the parent drug. In some cases, a prodrug may consist of two pharmacologically active drugs that are coupled together in a single molecule, so that each drug acts as a promoiety for the other. Such derivatives are called co-drugs.4 Prodrugs have also been called reversible or bioreversible derivatives, latentiated drugs, or biolabile drug-carrier conjugates, but the term “prodrug” is now standard. Some prodrugs lack an obvious carrier or promoiety, but result from a molecular modication of the active drug itself. This modication, which can be, for example, oxidation or reduction, generates a new active compound. These prodrugs are referred to as bioprecursor prodrugs. Finally, soft drugs also nd applications in tissue targeting. In contrast to prodrugs, soft drugs are active drugs but are designed to transform to an inactive form in vivo after achieving their therapeutic effect.5 The prodrug concept is illustrated in Figure 13.1.