title: Postprandial changes in solubilizing capacity of human intestinal fluids for BCS class II drugs.
abstract: OBJECTIVE
  To explore the effect of the nutritional state on the solubilizing properties of human intestinal fluids (HIF) on a time-after-food administration basis.
  
  
  METHODS
  HIF were collected in fractions of 30 min from five volunteers in the fasted, fed and fat-enriched fed state. In vitro solubility of five BCS class II drugs (danazol, diazepam, nifedipine, ketoconazole, indomethacin) was assessed in the intestinal fractions and simulated intestinal fluids.
  
  
  RESULTS
  Solubilities in intestinal fractions were characterized by high time- and subject-dependent variability. For the non-ionized drugs, solubility in early intestinal fractions was higher in both fed states compared to the fasted state, and in the fat-enriched fed state compared to the fed state. Solubility in simulated intestinal fluids did not sufficiently predict the solubilizing capacity of the early postprandial phase. Solubility in HIF was shown to be determined by a complex interplay of various intraluminal parameters. For the ionized drugs, pH played a significant role for indomethacin (R (2) = 0.86); for the partly ionized ketoconazole other intraluminal parameters were also important.
  
  
  CONCLUSIONS
  Solubilizing capacity of HIF in the fed state is strongly time-dependent. Intraluminal dissolution may, therefore, vary with drug arrival time in the small intestine and constitute a source of variability in intestinal drug absorption.
authors.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, Campus Gasthuisberg O&N 2, Herestraat 49, Leuven, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Clarysse
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Psachoulias
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.forename: Pieter
authors.initials: P
authors.lastname: Annaert
authors.forename: Guus
authors.initials: G
authors.lastname: Duchateau
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D004032:Diet; D004386:Duodenum / Q000502:physiology*; D005260:Female; D018565:Food-Drug Interactions; D005766:Gastrointestinal Contents / Q000737:chemistry*; D006801:Humans; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D019518:Postprandial Period; D012995:Solubility; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations