{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:56:01Z","timestamp":1791320161487,"version":"4.3.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>Donanemab is an amyloid\u2010targeting therapy that resulted in robust amyloid plaque reduction and slowed Alzheimer's disease (AD) progression compared with placebo in the phase II TRAILBLAZER\u2010ALZ study (NCT03367403). The objectives of the current analyses are to characterize (i) the population pharmacokinetics of donanemab, (ii) the relationship between donanemab exposure and amyloid plaque reduction (response), and (iii) the relationship between donanemab exposure and amyloid\u2010related imaging abnormalities with edema or effusions (ARIA\u2010E). Model development included data from participants with mild cognitive impairment or mild to moderate dementia due to AD from the phase Ib study on donanemab (NCT02624778) and participants with early symptomatic AD from the TRAILBLAZER\u2010ALZ study. The analysis showed donanemab has a terminal elimination half\u2010life of 11.8\u2009days. Body weight and antidrug antibody titer impact donanemab exposure but not the pharmacodynamic response. Maintaining a donanemab serum concentration above 4.43\u2009\u03bcg\/mL (95% confidence interval: 0.956, 10.4) is associated with amyloid plaque reduction. The time to achieve amyloid plaque clearance (amyloid plaque level &lt;\u200924.1 Centiloids) varied depending on the baseline amyloid level, where higher baseline levels were associated with fewer participants achieving amyloid clearance. The majority of participants achieved amyloid clearance by 52\u2009weeks on treatment. Apolipoprotein \u03b54 carriers, irrespective of donanemab serum exposure, were 4 times more likely than noncarriers to have an ARIA\u2010E event by 24\u2009weeks.<\/jats:p>","DOI":"10.1002\/cpt.2875","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T13:46:32Z","timestamp":1676727992000},"page":"1258-1267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Donanemab Population Pharmacokinetics, Amyloid Plaque Reduction, and Safety in Participants with Alzheimer's Disease"],"prefix":"10.1111","volume":"113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-8924","authenticated-orcid":false,"given":"Ivelina","family":"Gueorguieva","sequence":"first","affiliation":[{"name":"Eli Lilly and Company Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-8400","authenticated-orcid":false,"given":"Brian A.","family":"Willis","sequence":"additional","affiliation":[{"name":"Former Employee of Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyi","family":"Chua","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay","family":"Chow","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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