title: Restoration of rat colonic epithelium after in situ intestinal instillation of the absorption promoter, sodium caprate.
abstract: BACKGROUND
  Sodium caprate (C10) is an oral absorption promoter that is currently in clinical trials as a component of solid dosage forms for poorly permeable small molecules and peptides. Clinical data with zoledronic acid tablets suggest that significant delivery along with acceptable safety can be achieved from a once-a-week dosing regime. C10 has surfactant-like properties at the high doses used in vivo and therefore we examined its effects on rat intestinal epithelium following intestinal instillation.
  
  
  RESULTS
  Addition of 100 mM concentrations of C10 with the paracellular flux marker, fluorescein isothiocyanate-dextran 4 kDa, permitted a bioavailability of 33% to be achieved. When C10 was added 10, 30 and 60 min in advance of fluorescein isothiocyanate-dextran 4 kDa, enhancement still occurred, but was progressively reduced. Histology revealed that the permeability increase was likely related in part to superficial epithelial damage caused in the first few minutes of exposure, which was rapidly repaired within 30-60 min.
  
  
  CONCLUSIONS
  Design of optimized dosage forms containing C10 should corelease the payload and promoter close to the epithelium in high concentrations. While C10 induces some epithelial damage, its remarkable capacity for epithelial repair may render this effect insignificant in vivo.
authors: UCD School of Agriculture, Food Science and Veterinary Medicine, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Xuexuan
authors: X
authors: Wang
authors: Sam
authors: S
authors: Maher
authors: David J
authors: DJ
authors: Brayden
mesh_terms: D000818:Animals; D001682:Biological Availability; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003652:Decanoic Acids / Q000008:administration & dosage* / Q000633:toxicity; D003911:Dextrans / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000633:toxicity
chemical_list: D003652:Decanoic Acids; D003911:Dextrans; D005456:Fluorescent Dyes; D013501:Surface-Active Agents; C015219:fluorescein isothiocyanate dextran; C031071:decanoic acid; D016650:Fluorescein-5-isothiocyanate