{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:25:42Z","timestamp":1789475142595,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"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":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lecanemab (Leqembi\u00ae) was recently approved by health authorities in the United States, Japan, and China to treat early Alzheimer's disease (AD), including patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease upon confirmation of amyloid beta pathology. Extensively and sparsely sampled PK profiles from 1619\u2009AD subjects and 21,929 serum lecanemab observations from two phase I, one phase II, and one phase III studies were well characterized using a two\u2010compartment model with first\u2010order elimination. The final PK model quantified covariate effects of body weight and sex on clearance and central volume of distribution, ADA\u2010positive status, and albumin on clearance, and of Japanese ethnicity on central and peripheral volumes of distribution. Exposure to lecanemab was comparable between two lecanemab\u2010manufacturing processes. However, none of the identified covariates in the model had a clinically relevant impact on model\u2010predicted lecanemab\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    or AUC at steady state following 10\u2009mg\/kg bi\u2010weekly. Importantly, age, a well\u2010recognized risk factor for AD, was not found to significantly affect lecanemab PK. The incidence of ARIA\u2010E as a function of lecanemab exposure was modeled using a logit function with data pooled from 2641 subjects from the phase II and phase III studies, in which a total of 177 incidences of ARIA\u2010E were observed. The probability of ARIA\u2010E was significantly correlated with model\u2010predicted\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and predicted to be higher in subjects homozygous for\n                    <jats:italic>APOE4<\/jats:italic>\n                    . The incidence of isolated ARIA\u2010H was not associated with lecanemab exposure and was similar between placebo and lecanemab\u2010treated subjects.\n                  <\/jats:p>","DOI":"10.1002\/psp4.13224","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T08:38:46Z","timestamp":1724920726000},"page":"2111-2123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Population pharmacokinetics and exposure\u2013response analyses of safety (\n                    <scp>ARIA<\/scp>\n                    \u2010E and isolated\n                    <scp>ARIA<\/scp>\n                    \u2010H) of lecanemab in subjects with early Alzheimer's disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3481-1138","authenticated-orcid":false,"given":"Oneeb","family":"Majid","sequence":"first","affiliation":[{"name":"Eisai Ltd.  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