| Title | Prodrugs | |
| Author | Charalambos T. Plessas¹ and Achilles Benakis²
1. PHARMAKON Press Information Services, Athens, Greece 2. Laboratory of Drug Metabolism, Department of Pharmacology, University of Geneva, Switzerland |
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| Citation | Plessas, C.T., Benakis, A.: Prodrugs, Epitheorese Klin. Farmakol. Farmakokinet. 2(1): 3-16 (1988) | |
| Publication Date | 1988-07 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
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| Keywords | Prodrugs, drugs, metabolism, overcoming pharmacokinetic barriers, overcoming pharmaceutical barriers, structure-activity relationships, SAR, structure-toxicity relationships, STR, structure-metabolism relationships, SMR. | |
| Other Terms | review article | |
| Summary | Prodrugs are chemical derivatives inactive per se which must undergo in vivo chemical transformation prior to exerting their pharmacological or therapeutic action. They are designed to overcome pharmaceutical “barriers” (e.g. unpleasant taste or odour, pain on injection, gastrointestinal irritability, poor solubility, instability, slow dissolution rate) and/or pharmacokinetic (e.g. poor bioavailability, short or prolonged duration of action, high first-pass metabolism, toxicity or side effects, non-specificity or poor site specificity) associated with the parent drug molecule limiting the clinical usefulness of the drug. Prodrugs may be distinguished in carrier-linked (e.g. pilocarpic acid diesters, prodrugs of methyldopa), site-specific chemical delivery systems (e.g. dipivefrin, dopamine prodrugs) and bioprecursors (e.g. sulindac). Prodrug design involves structural modifications of lead compounds rationally deduced from qualitative and quantitative assessments of (a) structure-activity relationships; (b) structure-toxicity relationships, and (c) structure-metabolism relationships. Once the prodrug- task is complete, it is important for the prodrug to quantitatively convert to the drug. The site of this conversion and the methods used to evaluate success, depend upon the specific goal of the prodrug. The prodrugs presented in this review are representative of the different ways in which the prodrug concept has been approached to improve the clinical efficacy of various drugs. | |
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