{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:51:13Z","timestamp":1782489073401,"version":"3.54.5"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To determine the scaling factors required for inclusion of renal drug glucuronidation clearance in the prediction of total clearance via glucuronidation (CL<jats:sub>UGT<\/jats:sub>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Microsomal protein per gram of kidney (MPPGK) was determined for human \u2018mixed\u2019 kidney (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) microsomes (MKM). The glucuronidation activities of deferiprone (DEF), propofol (PRO) and zidovudine (AZT) by MKM and paired cortical (KCM) and medullary (KMM) microsomes were measured, along with the UGT 1A6, 1A9 and 2B7 protein contents of each enzyme source. Unbound intrinsic clearances (CL<jats:sub>int,u,UGT<\/jats:sub>) for PRO and morphine (MOR; 3\u2010 and 6\u2010) glucuronidation by MKM, human liver microsomes (HLM) and recombinant UGT1A9 and 2B7 were additionally determined. Data were scaled using<jats:italic>in vitro<\/jats:italic>\u2013<jats:italic>in vivo<\/jats:italic>extrapolation (IV\u2013IVE) approaches to assess the influence of renal CL<jats:sub>int,u,UGT<\/jats:sub>on the prediction accuracy of the calculated CL<jats:sub>UGT<\/jats:sub>values of PRO and MOR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MPPGK was 9.3\u00a0\u00b1\u00a02.0\u00a0mg\u00a0g<jats:sup>\u22121<\/jats:sup>(mean\u00a0\u00b1\u00a0SD). The respective rates of DEF (UGT1A6), PRO (UGT1A9) and AZT (UGT2B7) glucuronidation by KCM were 1.4\u2010, 5.2\u2010 and 10.5\u2010fold higher than those for KMM. UGT 1A6, 1A9 and 2B7 were the only enzymes expressed in kidney. Consistent with the activity data, the abundance of each of these enzymes was greater in KCM than in KMM. The abundance of UGT1A9 in MKM (61.3\u00a0pmol\u00a0mg<jats:sup>\u22121<\/jats:sup>) was 2.7 fold higher than that reported for HLM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Scaled renal PRO glucuronidation CL<jats:sub>int,u,UGT<\/jats:sub>was double that of liver. Renal CL<jats:sub>int,u,UGT<\/jats:sub>should be accounted for in the IV\u2013IVE of UGT1A9 and considered for UGT1A6 and 2B7 substrates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12889","type":"journal-article","created":{"date-parts":[[2016,1,25]],"date-time":"2016-01-25T19:58:43Z","timestamp":1453751923000},"page":"1153-1164","source":"Crossref","is-referenced-by-count":48,"title":["Scaling factors for the<i>in vitro<\/i>\u2013<i>in vivo<\/i>extrapolation (IV\u2013IVE) of renal drug and xenobiotic glucuronidation clearance"],"prefix":"10.1111","volume":"81","author":[{"given":"Kathleen M.","family":"Knights","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer, School of Medicine Flinders University Adelaide South Australia Australia 5001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane M.","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer, School of Medicine Flinders University Adelaide South Australia Australia 5001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1848-0121","authenticated-orcid":false,"given":"John K.","family":"Fallon","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmaceutics, Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuy","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer, School of Medicine Flinders University Adelaide South Australia Australia 5001"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Molecular Pharmaceutics, Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John O.","family":"Miners","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Flinders Centre for Innovation in Cancer, School of Medicine Flinders University Adelaide South Australia Australia 5001"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.128603"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02446.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(84)90133-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S0022-3565(25)38803-8","article-title":"Glucuronidation and sulfation in rabbit kidney","volume":"236","author":"Hjelle 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