title: Predicting human intestinal permeability using single-pass intestinal perfusion in rat.
abstract: OBJECTIVE
  The aim of the study was the prediction of human intestinal permeability and fraction absorbed of oral dose using single-pass intestinal perfusion technique (SPIP) in rats.
  
  
  METHODS
  Permeability coefficients in anaesthetized rats were determined for 14 compounds. Drug solution in phosphate buffered saline (PBS) was perfused through a ingle-pass intestinal perfusion (SPIP) with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. Phenol red was used as a non-absorbable marker to correct water flux through the segment. Drug concentrations in samples were determined using HPLC and permeability coefficients (Peff) were calculated.
  
  
  RESULTS
  The examined compounds demonstrated approximately 12.5 fold difference in magnitude for rat permeability coefficients among themselves. These values were compared with published data for human intestinal permeability, and a strong correlation was found between Peff (rat) and Peff (human); (Peff (human) = 11.04 Peff (rat) - 0.0003; R2= 0.93, P<0.0001). Subsequently the fraction dose absorbed in human (Fa) was estimated and predicted after oral dosing considering Fa(human)=1-e - 38450Peff(rat) (R2= 0.91, P<0.0001).
  
  
  CONCLUSIONS
  Considering the high correlation of rat Peff values with those of human we conclude that the SPIP could be utilized with precision to predict the human intestinal permeability. It may also be used as a reliable technique to predict the fraction of dose absorbed following oral administration of drug in solution or regular release dosage form in human.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Zakeri-Milani
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
authors.forename: Hosnieh
authors.initials: H
authors.lastname: Tajerzadeh
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Azarmi
authors.forename: Ziba
authors.initials: Z
authors.lastname: Islambolchilar
authors.forename: Saeed
authors.initials: S
authors.lastname: Barzegar
authors.forename: Mohammad
authors.initials: M
authors.lastname: Barzegar-Jalali
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005544:Forecasting; D006801:Humans; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010477:Perfusion / Q000379:methods; D010539:Permeability; D010599:Pharmacokinetics; D010637:Phenolsulfonphthalein; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D013045:Species Specificity
chemical_list: D010637:Phenolsulfonphthalein