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However, neither the expression of peptide transporter 1 (Pept1) nor the pharmacokinetics of Pept1 substrate drugs has been investigated under irinotecan\u2010induced gastrointestinal damage. Therefore, the present study quantitatively investigated the effects of irinotecan\u2010induced gastrointestinal damage on the intestinal expression of Pept1 and absorption of cephalexin (CEX), a typical Pept1 substrate, in rats. Irinotecan was administered intravenously to rats for 4\u00a0days to induce gastrointestinal damage. The expression of <jats:italic>Pept1<\/jats:italic> mRNA and the Pept1 protein in the upper, middle, and lower segments of the small intestine of irinotecan\u2010treated rats was assessed by quantitative real\u2010time polymerase chain reaction (PCR) and western blotting, respectively. The pharmacokinetic profile of CEX was examined after its oral or intravenous administration (10\u00a0mg\/kg). In irinotecan\u2010treated rats, \u223c2\u2010fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged. The oral bioavailability of CEX significantly decreased to 76% of that in control rats. The decrease in passive diffusion caused by intestinal damage may have overcome the increase in Pept1\u2010mediated uptake. In conclusion, irinotecan may decrease the intestinal absorption of Pept1 substrate drugs; however, it increased the expression of intestinal Pept1.<\/jats:p>","DOI":"10.1002\/bdd.2372","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T04:33:34Z","timestamp":1690605214000},"page":"372-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irinotecan\u2010induced gastrointestinal damage alters the expression of peptide transporter 1 and absorption of cephalexin in rats"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-0755","authenticated-orcid":false,"given":"Ayuko","family":"Imaoka","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacokinetics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoki","family":"Hattori","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacokinetics Keio University Faculty of Pharmacy  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-4465","authenticated-orcid":false,"given":"Takeshi","family":"Akiyoshi","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacokinetics Keio University Faculty of Pharmacy  Tokyo Japan"},{"name":"Department of Clinical Pharmacy School of Medicine Keio University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-9407","authenticated-orcid":false,"given":"Hisakazu","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacokinetics Keio University Faculty of Pharmacy  Tokyo Japan"},{"name":"Department of Clinical Pharmacy School of Medicine Keio University  Tokyo Japan"},{"name":"Department of Pharmacy Keio University Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.09.042"},{"issue":"14","key":"e_1_2_9_3_1","first-page":"3723","article-title":"Metabolic fate of irinotecan in humans: Correlation of glucuronidation with diarrhea","volume":"54","author":"Gupta E.","year":"1994","journal-title":"Cancer Research"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2205"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010008\u20109703\u20103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2006.05.020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.13\u201000255\u20101"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.60.1.0008"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010007\u20100534\u20104"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0378\u20105173(00)00563\u20109"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440\u20101681.2000.03380.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1020436028194"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0493"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.026922"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.42.6.1463"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.055939"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.1418"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00343.2016"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010006\u20100187\u20108"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016\u20105085(98)70585\u20102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40780\u2010021\u201000207\u2010w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1016086003070"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.12.023"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424\u2010005\u20100007\u20108"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0928\u20100987(03)00042\u20103"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1018982505021"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.2102"}],"container-title":["Biopharmaceutics &amp; 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