title: "Holistic" in silico methods to estimate the systemic and CNS bioavailabilities of potential chemotherapeutic agents.
abstract: A fundamental fact in the drug development process is that physical quantity of chemical substance is needed for experimental determinations. Information that could guide the course of a drug discovery program, in particular the penultimate ADME parameters % oral bioavailability (%F) and CNS permeability (BBB) are not explicitly determined until after large capital, human and time resources have been invested in a particular chemical series to produce the substance. To assure better go/no-go decisions and to protect the risks of a process that necessitates a considerable "front-loading" of resources, project teams are turning to computational methods to estimate these parameters. Herein we provide a detailed review of "holistic" in silico methods toward the estimation of %F and BBB. An unbiased description of the scope and limitations of their installation and application will be given in the context of an on going pharmaceutical project.
authors.affiliation: Paratek Pharmaceuticals, Inc, Boston, MA 02111, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Podlogar
authors.forename: I
authors.initials: I
authors.lastname: Muegge
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000378:metabolism*; D016208:Databases, Factual; D006801:Humans; D008962:Models, Theoretical; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations