The Pharmacology of Prodrugs of 5-Fluorouracil and 1-β-D-Arabinofuranosylcytosine

Abstract

This chapter discusses the pharmacology of prodrugs. The term prodrug was first introduced by Albert (1958); it refers to a chemically modified form of a drug, devoid of pharmacological activity, that must undergo transformation in a biological system to release the active form of the drug which then exerts the desired action. Such chemical modification to form compounds that rely on an enzymatic activation process has also been called drug latentiation. Since prodrugs are designed to be devoid of biological activity, and since their physicochemical properties differ from those of the parent drug up to the time of release of the active form, prodrugs often differ significantly from the parent molecule in their pharmacokinetic properties, thereby possessing the potential for favorable increase in delivery to the target site and/or decreased delivery to sensitive normal tissues. Thus, prodrug design has been used to overcome absorption problems, to improve membrane transport of drugs with poor lipid solubility, to assist in the stabilization of orally delivered agents, to offer sustained or prolonged release properties to drugs with short plasma half-lives, to reduce the toxic effects of agents, and to assist in site-specific delivery.