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However, ARBs have documented or suspected therapeutic properties in diseases not caused by high BP including diabetes, muscular dystrophy, chronic obstructive pulmonary diseases (COPD) and Alzheimer's disease. ARBs have multiple pleiotropic properties; \u2018\n                    <jats:italic>on\u2010target<\/jats:italic>\n                    \u2019 AT1\u2010dependent pleiotropy can arise from blocking AngII\u2010AT1 binding in non\u2010BP\u2010regulating cells or via inverse or biased ARB\u2010AT1 agonism. In addition, activation of cells lacking AT1 by ARBs suggests the presence of AT1\u2010independent \u2018\n                    <jats:italic>off\u2010target<\/jats:italic>\n                    \u2019 pleiotropy, whereas supratherapeutic properties in the absence of further BP lowering have also been reported. Herein, to determine how ARB pleiotropy and supratherapeutic properties can be modelled in\u00a0vitro or ex\u00a0vivo, we perform a retrospective analysis of the literature that characterizes their maximal human plasma concentration,\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    , which is higher and more likely to trigger pleiotropy than their low nanomolar, AT1\u2010blocking concentrations. Our findings suggest that\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    is variable and heterogeneous between ARBs, with upper range values as high as 13.6 micromolar in the case of valsartan and lower range values as low as 0.4 micromolar for candesartan. We propose that modelling of ARB pleiotropy be conducted at these concentrations, whereas higher concentrations will mimic supratherapeutic applications.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70203","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:02:01Z","timestamp":1773313321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Retrospective Analysis of Human Angiotensin II Receptor Blockers (ARB) Pharmacokinetics, Dosages and\n                    <i>C<\/i>\n                    <sub>max<\/sub>\n                    Values for the Experimental Modelling of Pleiotropic and Supratherapeutic Activities"],"prefix":"10.1111","volume":"138","author":[{"given":"Alexandria","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Pharmacology &amp; Therapeutics, and Centre for Heart + Lung Innovation, St. Paul's Hospital The University of British Columbia (UBC)  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bernatchez","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology &amp; Therapeutics, and Centre for Heart + Lung Innovation, St. Paul's Hospital The University of British Columbia (UBC)  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.02.174"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.05.051"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.10.023"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-2-18"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2017.03.007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283603f53"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.12626"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.1010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1137"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3521"},{"key":"e_1_2_11_12_1","first-page":"133","article-title":"Angiotensin II type I receptor blocker and endothelial function in humans: role of nitric oxide and oxidative stress","volume":"3","author":"Higashi Y.","year":"2005","journal-title":"Current Medicinal Chemistry. 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