In this chapter and in earlier writings (Stella 1996a, 2004), a case was made for continued prodrug research as a complementary tool in drug design. There are numerous unmet needs in prodrug research, such as novel strategies for overcoming presystemic metabolism (Johnson, 1980; Svensson and Tunek, 1988; Elger et al., 1995, 1998) and prodrug approaches to improve drug targeting. There is no question, supported by the relatively large percentage of recently approved drugs that are prodrugs, that prodrugs are being considered more and earlier as a solution to problems with poorly drugable molecules.

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