{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:50:26Z","timestamp":1790988626859,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2002,12,1]],"date-time":"2002-12-01T00:00:00Z","timestamp":1038700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In rats with acute renal failure induced by uranyl nitrate, the hepatic microsomal cytochrome P450 (CYP) 2E1 and CYP3A23 increased 2\u20134- and 4-times, respectively, CYP2C11 decreased to 80% of control, but the levels of CYP1A2 and CYP2B1\/2 were not changed. It has been reported that theophylline was metabolized to 1,3-dimethyluric acid by CYP1A2 and CYP2E1 and 1-methylxanthine via CYP1A2, which was metabolized further to 1-methyluric acid via xanthine oxidase in rats. Hence, it was expected that the formation of 1,3-dimethyluric acid would show an increase in rats with renal failure as a result of induction of CYP2E1. The pharmacokinetics of theophylline were compared in control rats and rats with renal failure after intravenous administration of aminophylline, 5 mg kg\u22121 as theophylline. In rats with renal failure, the plasma concentrations of theophylline were considerably lower and the resultant total area under the plasma concentration-time curve from time zero to time infinity (AUC0-\u221e) of theophylline was significantly smaller (2200 vs 1550 \u03bcg min mL\u22121) compared with control rats. In rats with renal failure, the plasma concentrations of 1,3-dimethyluric acid were considerably higher and the resultant AUC0\u20136 h of 1,3-dimethyluric acid was significantly greater (44.4 vs 456 \u03bcg min mL\u22121) compared with control rats. Moreover, the AUC0\u20136 h, 1,3-dimethyluric acid\/ AUC0\u2013\u221e, theophylline ratio increased from 2.02% in control rats to 29.4% in rats with renal failure. The in-vitro intrinsic 1,3-dimethyluric acid formation clearance was significantly faster in rats with renal failure (734 vs 529 10\u22126 mL min\u22121) compared with control rats using hepatic microsomal fraction. The results led us to conclude that in rats with uranyl nitrate-induced renal failure after the administration of aminophylline, 5 mg kg\u22121 as theophylline, there was an increase in the formation of 1,3-dimethyluric acid as a result of an increase in CYP2E1 expression.<\/jats:p>","DOI":"10.1211\/002235702333","type":"journal-article","created":{"date-parts":[[2003,1,24]],"date-time":"2003-01-24T03:38:08Z","timestamp":1043379488000},"page":"1687-1692","source":"Crossref","is-referenced-by-count":28,"title":["Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous theophylline in rats: the role of CYP2E1 induction in 1,3-dimethyluric acid formation"],"prefix":"10.1093","volume":"54","author":[{"given":"Su Yeon","family":"Yu","sequence":"first","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , San 56\u20131, Shinlim-Dong, Kwanak-Gu, Seoul 151\u2013742,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Chin","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , San 56\u20131, Shinlim-Dong, Kwanak-Gu, Seoul 151\u2013742,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , San 56\u20131, Shinlim-Dong, Kwanak-Gu, Seoul 151\u2013742,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Dentistry and Research Institute of Oral Science, Kangnung National University , 123 Chibyon-Dong, Kangnung, Kangwon-Do 210\u2013702,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inchull","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, College of Medicine, University of Ulsan, Asan Foundation, Asan Medical Center , 388\u20131 Poongnap-Dong, Songpa-Gu, Seoul 138\u2013736,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Geon","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , San 56\u20131, Shinlim-Dong, Kwanak-Gu, Seoul 151\u2013742,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Gull","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , San 56\u20131, Shinlim-Dong, Kwanak-Gu, Seoul 151\u2013742,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,12,1]]},"reference":[{"key":"2024103109383286000_cit1","first-page":"48","article-title":"Dose dependency of theophylline metabolism","volume":"8","author":"Birket","year":"1984","journal-title":"Clin. 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