Do prodrugs deliver?
This review examines the prodrug concept in the context of conventional prodrugs, which seek to increase systemic concentrations of a drug, and targeted prodrugs, which are designed to increase therapeutic ratio. In general, conventional prodrugs are designed to enhance oral absorption. With both types of prodrug, a pharmacokinetic/pharmacodynamic model must be created to understand the steps required and the barriers that need to be overcome to achieve success. This review highlights the role of polar surface area in identifying drugs that are suitable for oral absorption, and which have the required potency and retention at the intended site of pharmacology.
Smith
Dennis A
DA
Sandwich Laboratories, Pfizer Global Research and Development, Sandwich, Kent, CT13 9NJ, UK. dennis.a.smith@pfizer.com
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D014407:Tumor Cells, Cultured