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To estimate the impact of intestinal phase I and II metabolism on oral drug absorption, knowledge on the expression levels of the respective enzymes is an essential prerequisite. In addition, the potential interplay of metabolism and transport contributes to drug disposition. Both mechanisms may be subjected to coordinative regulation by nuclear receptors, leading to unwanted drug\u2010drug interactions due to induction of intestinal metabolism and transport. Thus, it was the aim of this study to comprehensively analyse the regional expression of clinically relevant phase I and II enzymes along the entire human intestine and to correlate these data to expression data of drug transporters and nuclear receptors of pharmacokinetic relevance. Gene expression of 11 drug\u2010metabolizing enzymes (\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2B6, 2C8, 2C9, 2C19, 2D6, 3A4, 3A5,\n                    <jats:styled-content style=\"fixed-case\">SULT<\/jats:styled-content>\n                    1A,\n                    <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n                    1A,\n                    <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n                    2B7, UGT2B15) was studied in duodenum, jejunum, ileum and colon from six organ donors by real\u2010time\n                    <jats:styled-content style=\"fixed-case\">RT<\/jats:styled-content>\n                    \u2010\n                    <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>\n                    . Enzyme expression was correlated with expression data of the nuclear receptors\n                    <jats:styled-content style=\"fixed-case\">PXR<\/jats:styled-content>\n                    ,\n                    <jats:styled-content style=\"fixed-case\">CAR<\/jats:styled-content>\n                    and\n                    <jats:styled-content style=\"fixed-case\">FXR<\/jats:styled-content>\n                    as well as drug transporters observed in the same cohort. Intestinal expression of all studied metabolizing enzymes was significantly higher in the small intestine compared to colonic tissue.\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2B6,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2C9,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2C19,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2D6,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    3A4\/5,\n                    <jats:styled-content style=\"fixed-case\">SULT<\/jats:styled-content>\n                    1A,\n                    <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n                    1A and\n                    <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n                    2B7 expression increased from the duodenum to jejunum but was markedly lower in the ileum. In the small intestine, that is, the predominant site of drug absorption, the highest expression has been observed for\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    3A4,\n                    <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>\n                    2C9,\n                    <jats:styled-content style=\"fixed-case\">SULT<\/jats:styled-content>\n                    1A and\n                    <jats:styled-content style=\"fixed-case\">UGT<\/jats:styled-content>\n                    1A. In addition, significant correlations were found between several enzymes and\n                    <jats:styled-content style=\"fixed-case\">PXR<\/jats:styled-content>\n                    as well as\n                    <jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content>\n                    transporters in the small intestine. In conclusion, the observed substantial site\u2010dependent intestinal expression of several enzymes may explain regional differences in intestinal drug absorption. The detected correlations between intestinal enzymes, transporters and nuclear receptors provide indirect evidence for their coordinative expression, regulation and function in the human small intestine.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.13137","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T12:10:21Z","timestamp":1537877421000},"page":"245-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Expression of clinically relevant drug\u2010metabolizing enzymes along the human intestine and their correlation to drug transporters and nuclear receptors: An intra\u2010subject analysis"],"prefix":"10.1111","volume":"124","author":[{"given":"Anja","family":"Fritz","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Center of Drug Absorption and Transport University Medicine Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Center of Drug Absorption and Transport University Medicine Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Lapczuk","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology Pomeranian Medical University Szczecin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of General and Transplantation Surgery Pomeranian Medical University Szczecin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Drozdzik","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology Pomeranian Medical University Szczecin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Oswald","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Center of Drug Absorption and Transport University Medicine Greifswald Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-016-9889-y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0351-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.01.001"},{"issue":"2","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0031-6997(24)01402-9","article-title":"Is the role of the small intestine in first\u2010pass metabolism overemphasized?","volume":"51","author":"Lin JH","year":"1999","journal-title":"Pharmacol Rev"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92302-I"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90177-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-9236(95)90168-X"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90162-9b"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920007782109788"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920021602150713114159"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.25.28"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404949200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.3.638"},{"issue":"10","key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0090-9556(25)08415-6","article-title":"The nifedipine\u2010rifampin interaction. 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