A Case for Prodrugs -- 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 -- Overcoming Poor Aqueous Solubility of Drugs for Oral Delivery -- Prodrugs and Parenteral Drug Delivery -- Poly (ethylene glycol) Prodrugs: Altered Pharmacokinetics and Pharmacodynamics -- Prodrugs to Reduce Presystemic Metabolism -- Controlled Release - Small Molecules -- Controlled Release - Macromolecular Prodrugs -- Controlled Release - Proenzymes -- Targeting - Theoretical and Computational Models -- Targeting - Cancer - Small Molecules -- Monoclonal Antibody Drug Conjugates for Cancer Therapy -- Antibody-Directed Enzyme Prodrug Therapy -- 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 - Preclinical and Clinical Considerations -- Prodrugs: Absorption, Distribution, Metabolism, Excretion (ADME) Issues -- Formulation Challenges of Prodrugs -- Safety Assessment of Prodrugs -- Toxicological Issues with Pivalate Prodrugs -- Case Studies -- Case Study: Adefovir Dipivoxil: An Oral Prodrug of Adefovir -- Case Study: Amifostine: (Ethyol®) -- Case Study: Capecitabine: A Prodrug of 5-Fluorouracil -- Case Study: Cefditoren Pivoxil: An Oral Prodrug of Cefditoren -- Case Study: Cefuroxime Axetil: An Oral Prodrug of Cefuroxime -- Case Study: Clindamycin 2-Phosphate, A Prodrug of Clindamycin -- Case Study: Enalapril: A Prodrug of Enalaprilat -- Case Study: Famciclovir: A Prodrug of Penciclovir -- Case Study: Fosamprenavir: A Prodrug of Amprenavir -- Case Study: Fosinopril -- Case Study: Fosphenytoin: A Prodrug of Phenytoin -- Case Study: Irinotecan (CPT-11), A Water-soluble Prodrug of SN-38 -- Case Study: Latanoprost: Isopropylester of a Prostaglandin F2? Analog -- Case Study: Moexipril Hydrochloride: A Prodrug of Moexiprilat -- Case Study: Mycophenolate Mofetil -- Case Study: Olmesartan Medoxomil: A Prodrug of Olmesartan -- Case Study: Omeprazole (Prilosec®) -- Case Study: Oseltamivir: An Orally Bioavailable Ester Prodrug of Oseltamivir Carboxylate -- Case Study: Parecoxib: A Prodrug of Valdecoxib -- Case Study: Tenofovir Disoproxil Fumarate: An Oral Prodrug of Tenofovir -- Case Study: Travoprost: A Potent PGF2? Analog -- Case Study: Valacyclovir: A Prodrug of Acyclovir -- Case Study: Valganciclovir: A Prodrug of Ganciclovir -- Case Study: Vantin: A Prodrug of Cefpodoxime -- Case Study: Ximelagatran: A Double Prodrug of Melagatran. 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.