Prodrug, definition

Prodrugs definitely will lead the way in novel delivery systems addressing the need for precise targeting and efficient delivery of cancer chemotherapeutics. The understanding of cellular mechanisms and continued advances in nanotechnology, material science, and engineering will continue to drive innovation in this field. 

V. J. Stella, Prodrugs An overview and definition, in Prodrugs in Novel Drug Delivery Systems (T. Higuchi and V. Stella, eds.), American Chemical Society, Washington, DC, 1975, p. 1. 

Prodrugs will receive much attention in this book (Chapt. 4, 6, 8, 9, and 11). It is, therefore, appropriate in this introductory chapter to clarify some definitions and review various aspects of prodrug design and research [11- 22],... 

So far no H3 ligand have been introduced into therapy, and we have to wait for results of clinical trials, which are in progress with the prodrug BP 2-94 (Rouleau et al., 1997), before the potential therapeutic usefulness of histamine H3 receptor ligands in peripheral diseases can be definitely assessed. 

Based on the definition of a prodrug, the following classifications may be proposed for oral prodrugs ... 

In a number of special cases, the above definitions of bioavailability are not directly applicable and singularly complicate the issue [4]. Thus, drugs having active metabolites present a special definitional challenge, particularly prodrugs (i.e., when most or all of the wanted effects are due to an active metabolite). Here, monitoring the... 

What makes prodrugs different from other drugs is the fact that they are devoid of intrinsic pharmacological activity. Thus, the simplest and clearest definition is the one given in 1958by Adrien Albert [16], who coined the term. In a modified form, the definition reads... 

A prodrug by definition is inactive or much less active and has to be converted to the active drug within the biological system. There are a variety of mechanisms by which a prodrug can be activated. These include metabolic activation mediated by enzymes present in the biological system as well as the less common, simple chemical means of activation such as hydrolysis. 

Iifitially, the term prodrug was introduced by Albert to describe any compound that undergoes biotransformation prior to exhibiting its pharmacological effects. Such a broad definition includes accidental historic prodrugs (salicin... 

Stella, V. Prodrugs an overview and definition. In Prodrugs as Novel Drug Delivery Systems (Higuchi, T., Stella, V., Eds), Vol. 14. American Chemical Society Washington, DC, 1975, pp. 1—115. 

Nomenclature is also a subject of confusion, although of much lesser importance than the metabolic aspects discussed in the previous paragraph. As examples of potential confusion some terms used in Europe are briefly discussed. A similar confrontation of definitions could also be made for other countries. The nomenclature adopted in 1965 (18)by the European Communities presents no problem for prodrugs ... 

In its Notice on "Studies of Prolonged-Action Forms in Man" dated 1987 09) the EC introduces the term of active principle presented in "pharmaceutical forms." This concept may apply to prodrugs, but only indirectly because the substance contained as such in the pharmaceutical form is not exactly the active principle. Similarly, in the council recommendation of 1987 on Investigation on Bioavailability (20), the terms active drug ingredient or therapeutic moiety of a drug are used to define the chemical species that should be measured. Finally, in a newer definition of bioavailability, the term active substance is used (21). 

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