{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:42:05Z","timestamp":1790743325103,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,9,30]],"date-time":"2013-09-30T00:00:00Z","timestamp":1380499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ther Apher Dial"],"published-print":{"date-parts":[[2014,4]]},"abstract":"Abstract<\/jats:title>Propranolol, the substrate of cytochrome P450<\/jats:styled-content> (CYP<\/jats:styled-content>) 1A2<\/jats:styled-content> and CYP2D6<\/jats:styled-content>, has been reported to be in high concentrations in end\u2010stage renal disease (ESRD<\/jats:styled-content>) patients. This has been thought to be due to the decrease in the nonrenal clearance of propranolol. The objective of this study is to elucidate the reason for the decrease in nonrenal clearance in ESRD<\/jats:styled-content> patients. CYP1A2<\/jats:styled-content> and CYP2D6<\/jats:styled-content> activities were estimated by the phenacetin O<\/jats:styled-content><\/jats:italic>\u2010deethylation and methoprolol O<\/jats:styled-content><\/jats:italic>\u2010demethylation methods, respectively. Pooled normal serum and pooled uremic serum were deproteinized by methanol in order to exclude high\u2010molecular\u2010weight compounds. We selected as candidate inhibitors: uremic toxins such as 3\u2010indoxyl sulfate, 3\u2010carboxy\u20104\u2010methyl\u20105\u2010propyl\u20102\u2010furanpropanoic acid, indole\u20103\u2010acetic acid, and hippuric acid, and xanthine derivatives such as allantoin, uric acid, and xanthine. In this study, uremic serum was found to inhibit the CYP1A2<\/jats:styled-content>\u2010mediated metabolism of phenacetin to acetaminophen in a concentration\u2010dependent and competitive manner. Xanthine also inhibited the metabolism of CYP1A2<\/jats:styled-content>. On the other hand, uremic serum and the four uremic toxins did not inhibit the CYP2D6<\/jats:styled-content>\u2010mediated metabolism of metoprolol to O<\/jats:styled-content><\/jats:italic>\u2010demethylmetoprolol. In conclusion, this study suggests that the increase of the bioavailability of propranolol in ESRD<\/jats:styled-content> is partly induced by the inhibition of the hepatic metabolism of CYP1A2<\/jats:styled-content> by xanthine in the uremic serum.<\/jats:p>","DOI":"10.1111\/1744-9987.12100","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:36:06Z","timestamp":1381541766000},"page":"174-180","source":"Crossref","is-referenced-by-count":11,"title":["Possibility of Decrease in CYP1A2<\/scp> Function in Patients With End\u2010Stage Renal Disease"],"prefix":"10.1111","volume":"18","author":[{"given":"Masayuki","family":"Tsujimoto","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Faculty of Pharmaceutical Science Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Faculty of Pharmaceutical Science Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Faculty of Pharmaceutical Science Kyoto Pharmaceutical University Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Furukubo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Service Shirasagi Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Service Shirasagi Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"Department of Medicine Shirasagi Hospital Osaka 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