Prodrugs

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.

Represents the first text of its kind, designed to give the reader a complete overview of prodrugs: the current status of the prodrug concept and its many applications and successes in overcoming formulation and delivery of problematic drugs

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 Delivery 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 (PrilosecÒ ).- 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