ABSTRACT
This chapter focuses on important issues in the design and development of prodrugs such as a different substrate specificities of human carboxylesterase isozymes and other hydrolases. Prodrugs such as acemetacin and indomethacin farnesyl have been developed to reduce the side effects of indomethacin. The prodrug enol-esterified with pivalic acid has an enol-containing alkoxy group and an acyl group having pivalic acid. Capecitabine is a prodrug developed to reduce the toxicity in bone marrow and the gastrointestinal tract, and it has a unique metabolic activation pathway. A prodrug in which an octanoyl group is introduced to the hydroxyl group at the 2- or 3-position of laninamivir is effective after inhaling only once at the time of onset and is used as a long-acting drug that is gradually metabolically activated. The prodrug enol-esterified with pivalic acid has an enol-containing alkoxy group and an acyl group having pivalic acid.
