{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:09:35Z","timestamp":1791461375932,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin\u20101 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary\u2010albumin\u2010to\u2010creatinine\u2010ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66\u2009years, median UACR 297\u2009mg\/g) after 4\u2009weeks treatment with 80\u2009mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC)\u00a0=\u00a0\u22120.64, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.046, median change UACR: \u221240.1%, 95% confidence interval (CI): \u221222.9 to \u221277.4%, mean telmisartan area under the curve (AUC)\u00a0=\u00a02927.1\u2009ng\u00b7hour\/mL, 95% CI: 723.0 to 6501.6\u2009ng\u00b7hour\/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin\u20101 RO in five patients with T2D (mean age 60\u2009years, median UACR 72\u2009mg\/g) in a separate positron emission tomography imaging study with [<jats:sup>11<\/jats:sup>C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC\u00a0=\u00a00.976, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.024). A meaningful RO could be calculated in three patients receiving 120\u2009mg oral telmisartan, and although high exposure seems related to higher RO, with AUC<jats:sub>0\u2013last<\/jats:sub> of 31, 840, and 274\u2009ng\u00b7hour\/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.<\/jats:p>","DOI":"10.1002\/cpt.2744","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T14:23:36Z","timestamp":1662560616000},"page":"1264-1270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Studying Telmisartan Plasma Exposure, Kidney Distribution, Receptor Occupancy, and Response in Patients With Type 2 Diabetes Using [<scp><sup>11<\/sup>C<\/scp>]Telmisartan"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-9337","authenticated-orcid":false,"given":"Sjoukje","family":"van der Hoek","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3715-6474","authenticated-orcid":false,"given":"Douwe J.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Division of Vascular Medicine, Department of Internal Medicine University Medical Center Groningen, University of Groningen  Groningen The\u00a0Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoon T.M.","family":"Willemsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Visser","sequence":"additional","affiliation":[{"name":"Symeres  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Heeres","sequence":"additional","affiliation":[{"name":"Symeres  Groningen The Netherlands"},{"name":"Hanze University of Applied Sciences  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riemer H.J.A.","family":"Slart","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip H.","family":"Elsinga","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiddo J.L.","family":"Heerspink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-9008","authenticated-orcid":false,"given":"Jasper","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"e_1_2_9_1_1","first-page":"1","volume-title":"International Diabetes Federation Diabetes Atlas, Ninth Edition","author":"International Diabetes Federation","year":"2019"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.06.019"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011303"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12655"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.26"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12149-011-0466-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1674-8301(12)60014-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2012.01.008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1271350"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127000004001202"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.121.262430"},{"key":"e_1_2_9_14_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2020"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/009127000004001210"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1928"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpcardio0806"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.08.034"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2744","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.2744","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.2744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:35:40Z","timestamp":1699364140000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.2744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/cpt.2744"],"URL":"https:\/\/doi.org\/10.1002\/cpt.2744","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]},"assertion":[{"value":"2022-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}