title: Biopharmaceutic classification of drugs revisited.
abstract: The biopharmaceutics classification system (BCS) was based on the tube model of the intestinal lumen. This model considers constant drug permeability along the intestines, a plug flow fluid with the suspended drug particles moving with the fluid, and dissolution in the small particle limit. Since then the research work focusing on drug gastrointestinal (GI) absorption phenomena and processes rely on the classical laws of transport, diffusion and kinetics; however, the homogeneous assumptions associated with the well-stirred Euclidean media, where the classical laws of diffusion and kinetics apply, have been questioned in the past. In this work we explore the biopharmaceutic classification of drugs using a heterogeneous pseudo steady-state model of oral drug absorption. The fraction of dose absorbed (Fabs) was expressed as a function of two time-dependent processes where time dependent coefficients govern drug absorption and non-absorption processes. Fundamental drug properties like the absorption potential are correlated with Fabsand allow the biopharmaceutic classification of drugs taking into account the heterogeneous aspects of oral drug absorption. This analysis reveals that for Class I drugs no time dependency is expected for both absorption and non absorption processes since the gastric emptying is controlling the absorption of Class I drugs while the completion of absorption (Fabs>90%) is terminated along the first part of the jejunum. Due to the biopharmaceutical properties of Class II, III and IV drugs, these drugs travel throughout the GI tract and therefore both absorption and non absorption processes will exhibit time dependency. Thus, the calculation of Fabs(<90%) for Class II, III and IV is dependent on the estimates of the time exponents of time dependent coefficients controlling drug absorption e.g. dissolution, uptake or non absorption e.g. precipitation.
authors: Laboratory of Biopharmaceutics & Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens 15771, Greece.
authors: Chrysa
authors: C
authors: Daousani
authors: Laboratory of Biopharmaceutics & Pharmacokinetics, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens 15771, Greece. Electronic address: macheras@pharm.uoa.gr.
authors: Panos
authors: P
authors: Macheras
mesh_terms: D001682:Biological Availability; D001702:Biopharmaceutics / Q000145:classification* / Q000379:methods*; D003198:Computer Simulation; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations
keywords: BCS; Fraction absorbed; Heterogeneous; Oral absorption; Variability