title: Elucidating the role of dose in the biopharmaceutics classification of drugs: the concepts of critical dose, effective in vivo solubility, and dose-dependent BCS.
abstract: OBJECTIVE
  To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose.
  
  
  METHODS
  We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose for the various classes of BCS and the marginal cases in between classes.
  
  
  RESULTS
  Simulations based on the mathematical model of F versus dose produced patterns of a constant F throughout a wide range of doses for drugs of Classes I, II and III, justifying biowaiver claim. For Classes I and III the pattern of a constant F stops at a critical dose Dose(cr) after which the amount of drug absorbed, is independent from the dose. For doses higher than Dose(cr), Class I drugs become Class II and Class III drugs become Class IV. Dose(cr) was used to define an in vivo effective solubility as S(eff) = Dose(cr)/250 ml. Literature data were used to support our simulation results.
  
  
  CONCLUSIONS
  A new biopharmaceutic classification of drugs is proposed, based on F, separating drugs into three regions, taking into account the dose, and Dose(cr), while the regions for claiming biowaiver are clearly defined.
authors: Laboratory of Biopharmaceutics & Pharmacokinetics Faculty of Pharmacy, National & Kapodistrian University of Athens, Athens, Greece.
authors: Georgia
authors: G
authors: Charkoftaki
authors: Aristides
authors: A
authors: Dokoumetzidis
authors: Georgia
authors: G
authors: Valsami
authors: Panos
authors: P
authors: Macheras
mesh_terms: D001702:Biopharmaceutics / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000145:classification; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations