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The exogenous probe substrate method, a minimally invasive approach to assess liver metabolic enzyme activity <jats:italic>in vivo<\/jats:italic>, is effective in studying these changes. Amlodipine being extensively metabolized (&gt;\u200990%) in the liver, primarily via cytochrome P450 enzyme CYP3A was selected as a probe to investigate and quantify the factors affecting the aging\u2010related changes of CYP3A in the Chinese older population. Amlodipine concentration data were collected from an ongoing noninterventional clinical study conducted at Peking University Third Hospital. A physiologically\u2010based pharmacokinetic modeling approach, grounded in population pharmacokinetic (PPK) analysis, was employed to physiologically quantify the aging\u2010related changes in CYP3A function. A total of 132 amlodipine concentrations from 69 patients were obtained from the clinical study. PPK analysis shows that frailty phenotype but not age is a significant influence and frail patients have 37% greater plasma amlodipine exposure than nonfrail patients. This difference in CYP3A function may be attributed to a 63.2% lower CYP3A relative abundance in the frail patients, compared with that in the nonfrail patients. In the context of dose selection for older adults, focusing on frailty rather than chronological age should be recognized as a more relevant approach, because frailty might more accurately reflect the individual's biological age. Our study suggested a need to shift the research focus from chronological age to biological age.<\/jats:p>","DOI":"10.1002\/cpt.3347","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T08:05:38Z","timestamp":1719043538000},"page":"858-865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Aging\u2010Related <scp>CYP3A<\/scp> Functional Changes in Chinese Older Patients: New Findings from Model\u2010Based Assessment of Amlodipine"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-7277","authenticated-orcid":false,"given":"Jie En","family":"Valerie Sia","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University  Shanghai China"},{"name":"Geriatrics Department Peking University Third Hospital  Beijing China"},{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Lai","sequence":"additional","affiliation":[{"name":"Geriatrics Department Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Yao","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Geriatrics Department Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6446-0127","authenticated-orcid":false,"given":"Cheng","family":"Cui","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"},{"name":"Center of Clinical Medical Research, Institute of Medical Innovation and Research Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0608-8192","authenticated-orcid":false,"given":"Dongyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"},{"name":"Center of Clinical Medical Research, Institute of Medical Innovation and Research Peking University Third Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Cardiovascular Receptors Research Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.08.013"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-015-0318-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544010-00002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(95)00192-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198461010-00006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/57.9.866"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(98)90106-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.122"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.055400"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4321\/S1130-01082012000400002"},{"key":"e_1_2_9_11_1","unstructured":"FDA US.NORVASC (amlodipine besylate) label. <https:\/\/wwwaccessdatafdagov\/drugsatfda_docs\/label\/2007\/019787s042lblpdf.2007>. 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