Computational methods to estimate drug development parameters

Computational methods are currently available to estimate oral bioavailability, solubility, metabolism, toxicity, pKa, blood-brain barrier permeability and other ADME and physicochemical parameters. Decisions as to which methods to implement and to employ must be made in accordance with the stated goals of a drug discovery organization, the timeline for these goals, and the budgetary limitations as set forth to accomplish these goals. Certain methods are more attractive to the production environment of a pharmaceutical project team where early ADME and Tox information is sought to aid in drug design decisions and prioritization. Practical limitations of these methods, ease of use, utility of results, as well as their scope and limitations are discussed. Recommendations as to which parameters are best estimated by commercial products, as opposed to those that can be developed in-house, are delineated. Special attention is given to those methods that can be integrated into the current high-throughput paradigms of drug discovery programs. Together, these considerations define a 'zero-infrastructure' approach to provide ADME and Tox information during the early stages of the drug design process.