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Moreover, existing <jats:italic>in vitro<\/jats:italic> models do not take into consideration that the intestine is heterogeneous with respect to P\u2010gp expression. Recently, we reported rat precision\u2010cut intestinal slices (PCIS) as a physiological <jats:italic>ex vivo<\/jats:italic> model to study the regional gradient of P\u2010gp activity and inhibition. Here we extended the application of PCIS to the human intestine. For this purpose rhodamine 123 (R123) accumulation in the presence or absence of the P\u2010gp inhibitors verapamil, cyclosporine A, quinidine, ketoconazole, PSC833 and CP100356 was measured in PCIS of human duodenum, jejunum, ileum and colon. R123 accumulation in the presence of the P\u2010gp inhibitors appeared to be most enhanced in the ileum compared to the other regions. Moreover, the regional differences in accumulation are in line with published differences in abundance of P\u2010gp. The rank order of the potency of the P\u2010gp inhibitors, reflected by their IC<jats:sub>50<\/jats:sub>, was comparable to that in rat PCIS. However, the increase in accumulation of the P\u2010gp substrate R123 by the inhibitors was larger in human ileum PCIS than in rat PCIS, indicating species difference in P\u2010gp abundance. These data show that human PCIS are an appropriate <jats:italic>ex vivo<\/jats:italic> model to study the activity of intestinal P\u2010gp and predict the inhibitory effect of drugs and of transporter\u2010mediated drug\u2010drug interactions in the human intestine. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/bdd.2047","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T07:06:41Z","timestamp":1476860801000},"page":"127-138","source":"Crossref","is-referenced-by-count":20,"title":["P\u2010gp activity and inhibition in the different regions of human intestine <i>ex vivo<\/i>"],"prefix":"10.1002","volume":"38","author":[{"given":"Ming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pharmacokinetics, Toxicology &amp; Targeting Groningen Research Institute of Pharmacy, University of Groningen  Antonius Deusinglaan 1, 9713 AV Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge A.M.","family":"de Graaf","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Toxicology &amp; Targeting Groningen Research Institute of Pharmacy, University of Groningen  Antonius Deusinglaan 1, 9713 AV Groningen the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina H.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Toxicology &amp; 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