Prodrugs

by Stella, Valentino J.; Borchardt, Ronald T.; Hageman, Michael J.; Oliyai, Reza; Maag, Hans

• ISBN13: 9780387497822
• ISBN10: 038749782X
• Edition: 1st
• Format: Hardcover
• Copyright: 2007-03-12
• Publisher: Amer Assn of Pharmaceutical

Summary

Prodrugs are substances administered in an inactive form that is then metabolized in the body in vivo into the active compound. The rationale behind administering prodrugs is to optimize absorption, distribution, metabolism, and excretion of these drugs. Since first described in the 1950s, prodrugs continue to be a fertile area of research. There are a number of small pharmaceutical/biotech companies dedicated to using prodrugs for the delivery of older but problematic drugs as well as to developing broad-based prodrug technologies for application to new and future drugs. These volumes represent a comprehensive guide to prodrugs and will guide the reader through the current status of the prodrug concept and its many applications and to highlight its many successes in overcoming formulation and delivery of problematic drugs.

Table of Contents

A Case for Prodrugs

Problems Addressable by Prodrugs

Prodrug Approaches to Enhancing the Oral Delivery of Poorly Permeable Drugs

Topical Delivery Using Prodrugs

Prodrug Approaches to Ophthalmic Drug Delivery

Oral Delivery

Prodrugs and Parenteral Drug Delivery

Poly (ethylene glycol) Prodrugs: Altered Pharmacokinetics and Pharmacodynamics

Prodrugs to Reduce Presystemic Metabolism

Small Molecules

Controlled Release - Macromolecular Prodrugs

Proenzymes

Targeting: Theoretical and Computational Models

Cancer'Small Molecules

Monoclonal Antibody Drug Conjugates for Cancer Therapy

Antibody-Directed Enzyme Prodrug Therapy (ADEPT)

Prodrugs for Liver-Targeted Drug Delivery

Prodrug Approaches for Drug Delivery to the Brain

Lymphatic Absorption of Orally Administered Prodrugs

Colonic Deliver?

Functional Group Approach to Prodrugs

Prodrugs of Carboxylic Acids

Prodrugs of Alcohols and Phenols

Prodrugs of Amines

Prodrugs of Amides, Imides and Other NH-Acidic Compounds

Prodrugs of Benzamidines

Prodrugs of Phosphonates, Phosphinates, and Phosphates

Functional Group Approaches to Prodrugs: Functional Groups in Peptides

Macromolecular Prodrugs of Small Molecules

Miscellaneous Functional Groups

Prodrugs: Absorption, Distribution, Metabolism, Excretion (ADME) Issues

Formulation Challenges of Prodrugs

Safety Assessment of Prodrugs

Toxicological Issues with Pivalate Prodrugs

Adefovir Dipivoxil: An Oral Prodrug of Adefovir

Amifostine: (Ethyol")

Capecitabine: A Prodrug of 5-Flurouracil

Cefditoren Pivoxil: An Oral Prodrug of Cefditoren

Cefuroxime Axetil: An Oral Prodrug of Cefuroxime

Clindamycin 2-Phosphate: A Prodrug of Clindamycin

Enalapril: A Prodrug of Enalaprilat

Famciclovir: A Prodrug of Penciclovir

Fosamprenavir: A Prodrug of Amprenavir

Fosinopril

Fosphenytoin: A Prodrug of Phenytoin

Irinotecan (CPT-11), A Water-soluble Prodrug of SN-38

Latanoprost: Isopropylester of a Prostaglandin F2a Analog

Moexipril Hydrochloride: A Prodrug of Moexiprilat

Mycophenolate Mofetil

Olmesartan Medoxomil: A Prodrug of Olmesartan

Omeprazole (Prilosec)

Oseltamivir: An Orally Bioavailable Ester Prodrug of Oseltamivir Carboxylate

Parecoxib: A Prodrug of Valdecoxib

Tenofovir Disoproxil Fumarate: An Oral Prodrug of Tenofovir

Travoprost: A Potent PGF2a Analog

Valacyclovir: A Prodrug of Acyclovir

Valganciclovir: A Prodrug of Ganciclovir

Vantin: A Prodrug of Cefpodoxime

Ximelagatran: A Double Prodrug of Melagatran

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