A Physical Chemical Basis for the Design of Orally Active Prodrugs

Abstract

Publisher Summary This chapter discusses the physical chemical basis for the design of orally active prodrugs. The rational design of prodrugs having oral biological activity can be divided into three basic steps: the determination of the physical properties required for maximum efficacy, the selection of a chemical linkage between the parent drug and the pro-moiety that will be cleaved in the desired biological compartment, and the design and synthesis of prodrugs that have the proper physical-chemical properties and the proper chemical lability. The selection of optimum physical–chemical parameters is accomplished through the aid of in vitro and in vivo experimentation and modeling. If the biological system is clearly understood, it is usually possible to devise models that can give reliable estimates of what physical–chemical parameters are important and of their optimal values. These conclusions can often be verified by studies on the uptake of model compounds into the tissues or circulation of lower animals.