title: Potential role of intestinal first-pass metabolism in the prediction of drug-drug interactions.
abstract: BACKGROUND
  The contribution of intestine to the magnitude of drug-drug interactions (DDI) may be significant, considering high levels of inhibitors in the gut lumen achieved during absorption and the abundance of metabolic enzymes in the mature enterocytes. Intestinal inhibition is incorporated in the DDI prediction models as the ratio of the intestinal wall availability in the presence and absence of the inhibitor (F(G)(') and F(G), respectively).
  
  
  OBJECTIVE
  This review will focus on the ability of the current approaches to estimate the extent of intestinal DDI accurately, addressing predominantly the most abundant intestinal P450 enzyme, CYP3A4.
  
  
  METHODS
  Considering the sensitivity of the DDI prediction models to the accuracy of the F(G) estimates, the current study focuses on 3 different in vitro and in vivo approaches to assess this parameter.
  
  
  CONCLUSIONS
  The advantages and limitations of each of F(G) methods are outlined. Accurate assessment of this parameter is essential for the prediction of human drug clearance and drug-drug interaction potential.
authors.affiliation: University of Manchester, School of Pharmacy and Pharmaceutical Sciences, Oxford Road, Manchester, M13 9PT, UK. Aleksandra.Galetin@manchester.ac.uk
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Galetin
authors.forename: Michael
authors.initials: M
authors.lastname: Gertz
authors.forename: J Brian
authors.initials: JB
authors.lastname: Houston
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System