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The aim of this study was to use this PBPK model to assess the magnitude of drug\u2013drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta\u2010analyses of literature data suggested that the abundance of UGT2B7 and the BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the CYP3A4 abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration\u2013time profile for mirabegron in an sRI population (simulated area under the plasma concentration\u2013time curve (AUC) was within 1.5\u2010times that of the observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a CYP3A4 inhibitor) was 4.12\u2010times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a CYP2D6 substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.<\/jats:p>","DOI":"10.1002\/bdd.2181","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T14:41:34Z","timestamp":1555339294000},"page":"176-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Application of a physiologically based pharmacokinetic model for the prediction of mirabegron plasma concentrations in a population with severe renal impairment"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-7736","authenticated-orcid":false,"given":"Kentaro","family":"Konishi","sequence":"first","affiliation":[{"name":"Analysis &amp; Pharmacokinetics Research Laboratories Drug Discovery Research, Astellas Pharma Inc.  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Minematsu","sequence":"additional","affiliation":[{"name":"Analysis &amp; Pharmacokinetics Research Laboratories Drug Discovery Research, Astellas Pharma Inc.  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhisa","family":"Nagasaka","sequence":"additional","affiliation":[{"name":"Analysis &amp; Pharmacokinetics Research Laboratories Drug Discovery Research, Astellas Pharma Inc.  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tabata","sequence":"additional","affiliation":[{"name":"Analysis &amp; Pharmacokinetics Research Laboratories Drug Discovery Research, Astellas Pharma Inc.  Ibaraki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,5,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/187231209788654081"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/74.4.452"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.17.2038"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-012-0031-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.163"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/11534750-000000000-00000"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-016-0350-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/75.1.31"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2013.02.077"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/2193-9616-1-9"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425250802691074"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2012.10.016"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01667018"},{"key":"e_1_2_10_16_1","article-title":"Physiologically\u2010based pharmacokinetic modeling for mirabegron: a multi\u2010elimination pathway mediated by cytochrome P450 3A4, uridine 5\u2032\u2010diphosphate\u2010glucuronosyltransferase 2B7, and butyrylcholinesterase","author":"Konishi K.","year":"2018","journal-title":"Xenobiotica"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-017-0450-x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-013-0133-1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2012.09.010"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-013-0084-y"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2012.08.019"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00365.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/72.4.497-a"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1984.89"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12194"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.59"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010510-100540"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.10.143"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000102971.85504.7c"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1013"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1989.125"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.05.010"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.115840"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp300582s"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2012.675095"},{"key":"e_1_2_10_36_1","unstructured":"U.S. Food and Drug Administration. 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