title: A semi-mechanistic modeling strategy for characterization of regional absorption properties and prospective prediction of plasma concentrations following administration of new modified release formulations.
abstract: OBJECTIVE
  To outline and test a new modeling approach for prospective predictions of absorption from newly developed modified release formulations based on in vivo studies of gastro intestinal (GI) transit, drug release and regional absorption for the investigational drug AZD0837.
  
  
  METHODS
  This work was a natural extension to the companion article "A semi-mechanistic model to link in vitro and in vivo drug release for modified release formulations". The drug release model governed the amount of substance released in distinct GI regions over time. GI distribution of released drug substance, region specific rate and extent of absorption and the influence of food intake were estimated. The model was informed by magnetic marker monitoring data and data from an intubation study with local administration in colon.
  
  
  RESULTS
  Distinctly different absorption properties were characterized for different GI regions. Bioavailability over the gut-wall was estimated to be high in duodenum (70%) compared to the small intestine (25%). Colon was primarily characterized by a very slow rate of absorption.
  
  
  CONCLUSIONS
  The established model was largely successful in predicting plasma concentration following administration of three newly developed formulations for which no clinical data had been applied during model building.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24, Uppsala, Sweden. martin.bergstrand@farmbio.uu.se
authors.forename: Martin
authors.initials: M
authors.lastname: Bergstrand
authors.forename: Erik
authors.initials: E
authors.lastname: Söderlind
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Eriksson
authors.forename: Werner
authors.initials: W
authors.lastname: Weitschies
authors.forename: Mats O
authors.initials: MO
authors.lastname: Karlsson
mesh_terms: D000328:Adult; D000578:Amidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000991:Antithrombins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001384:Azetidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000737:chemistry*; D041981:Gastrointestinal Tract / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D055815:Young Adult
chemical_list: C551586:AZD 0837; D000578:Amidines; D000991:Antithrombins; D001384:Azetidines; D003692:Delayed-Action Preparations