Prodrugs objective

Prodrug design aims to overcome a number of barriers to a drug s usefulness (Table 1.1). Based on these and other considerations, the major objectives of prodrug design can be listed as also shown in Table 1.1. 

These objectives in the design of prodrugs will be discussed in more detail in the context of Chapt. 8 (carboxylic acid prodrugs) and 11 (various hydrolyzable groups). 

This book has had as its first objective a comprehensive and systematic presentation of hydrolytic reactions in the metabolism of drugs, prodrugs, and other xenobiotics. As such, it aims to fulfill a utilitarian and an educa-... 

General design objective Goal Drug Prodrug... 

Table 1 Barriers to drug usefulness and corresponding objectives of prodrug design...

The concepts and examples presented here are meant to clarify the objectives of a prodrug strategy, to exemplify the major chemical moieties used in prodrug design, and to illustrate the biochemical pathways involved in prodrug activation (i.e., hydrolysis, oxidation, or reduction). More detailed information can be found in a number of reviews [1-15]. 

Although many prodrug studies in the literature bring useful information on activation mechanisms and structure-metabolism relation, they do not appear to address a genuine clinical need. In contrast, many other studies do attempt to improve some properties of a marketed drug ora drug candidate under development. As detailed below, the target properties to be improved (i.e., the objectives) may be pharmaceutical, pharmacokinetic, or pharmacodynamic. A summary of these objectives is presented in Table 20.1. 

Bernard Testa Introduction 559 Why Prodrugs 560 Pharmaceutical Objectives 560... 

A less frequent but nonetheless interesting problem arises in the chemical modification of liquid, or low-melting, active principles in solid prodrugs, suitable for tablet or capsule preparation. Indeed solid dosage forms are still the most widely used for the administration of medicines, as well for patient acceptability and convenience for product stability and ease of manufacture. Their preparation implies that the active principle can itself be handled as a stable solid, an objective that is usually attained by one of the following strategies formation of a salt or a molecular complex, formation of a crystalline covalent derivative, introduction of symmetry. 

Acyl enzymes have recently become objects of pharmacological interest as potential prodrugs. This is best illustrated by the following propositions ... 

However, thus far, only the prodrug approach seems to have met objectives that allow commercialization of such ophthalmic products. 

---