In general, prodrug research begins with careful selection of pro-moieties to be conjugated to the parent molecule. A number of structural classes of pro-moieties are available for prodrug derivatization with information on enzymatic or non-enzymatic activation of prodrugs to the parent drugs . Once a prodrug derivative that affords a promise in correcting the pharmacokinetic limitation of the parent drug is found, further optimization efforts may follow for most favorable physico-chemical and pharmacokinetic properties.
During the past few years, significant progress has been achieved in oral prodrug discovery research. In particular, rational prodrug design has been more frequently practiced because of increased understanding of the complex functions of the intestinal epithelium in the drug absorption process. Furthermore, selective delivery of active parents to target sites has been pursued through the exploitation of tissue-specific transporters and metabolic enzymes for prodrugs. Other innovative applications of prodrugs, such as prolongation of plasma half-life, have also been realized. Structurally, a number of new useful pro-moieties have been discovered from these recent efforts, broadening the scope of prodrug derivatizations. This chapter will provide an update on the progress of oral prodrug research, with illustration of recent examples of prodrug derivatives. Several previous reviews concerning oral prodrug approaches can also be consulted for further information [2-7].
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