title: Rate- and Extent-Limiting Factors of Oral Drug Absorption: Theory and Applications.
abstract: The oral absorption of drugs has been represented by various concepts such as the absorption potential, the maximum absorbable dose, the biopharmaceutics classification system, and in vitro-in vivo correlation. The aim of this article is to provide an overview of the theoretical relationships between these concepts. It shows how a simple analytical solution for the fraction of a dose absorbed (Fa equation) can offer a theoretical base to tie together the various concepts, and discusses how this solution relates to the rate-limiting cases of oral drug absorption. The article introduces the Fa classification system as a framework in which all the above concepts were included, and discusses its applications for food effect prediction, active pharmaceutical ingredient form selection, formulation design, and biowaiver strategy.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, 274-8510, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Sugano
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, 274-8510, Japan.
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001702:Biopharmaceutics / Q000145:classification; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D009061:Mouth Mucosa / Q000378:metabolism*
keywords: bioequivalence; biopharmaceutics classification system (BCS); dissolution; food effects; formulation; gastrointestinal transit; in silico modeling; intestinal absorption; oral absorption; salt selection