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While the pharmacokinetics of daily rapamycin are well-characterized in transplant populations, limited data exist on intermittent dosing regimens in patients with neurodegenerative conditions.\u00a0This open-label pilot study investigated the pharmacokinetic properties of weekly oral rapamycin in 13 patients with early-stage AD. Participants received 7\u00a0mg weekly (11 patients) or reduced doses (2\u00a0mg and 4\u00a0mg; 2 patients) for 26\u00a0weeks. Blood concentrations were measured at four timepoints (pre-dose\/Cmin, and 1-, 3-, and 48-h post-dose) during week 13.\u00a0Moderate interindividual variability was observed across timepoints (coefficient of variation was 0.28\u20130.40), with the 48-h sample showing the lowest variability (CoV\u2009=\u20090.28) and strongest correlation with Cmin from the previous dosing (r\u2009=\u20090.72). Estimate of terminal half-life (68.9\u2009\u00b1\u200913.6\u00a0h) aligned with previous studies.\u00a0Blood concentrations at Cmin were below immunosuppressive levels in all participants. Our findings suggest that weekly rapamycin administration in AD patients results in acceptable pharmacokinetic variability, supporting fixed-dose regimens in future trials. The 48-h post-dose measurement appears optimal for monitoring blood concentrations. Additionally, our investigation into cerebrospinal fluid rapamycin quantification revealed methodological challenges due to analytical sensitivity limitations. The foremost limitation of this study was the sparse blood sampling schedule, with Cmin collected from the previous dosing occasion which prevented a complete AUC-calculation.\u00a0ClinicalTrials.gov (NCT06022068) and EudraCT (2023\u2013000127\u201336).<\/jats:p>","DOI":"10.1007\/s11357-025-01911-3","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T22:51:31Z","timestamp":1759618291000},"page":"3295-3304","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease"],"prefix":"10.1007","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1151-5691","authenticated-orcid":false,"given":"Helen Annervik","family":"Wallgren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia","family":"Kivipelto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pontus","family":"Plav\u00e9n-Sigray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-4913","authenticated-orcid":false,"given":"Jonas E.","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,5]]},"reference":[{"issue":"1","key":"1911_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s40643-022-00554-y","volume":"9","author":"MA Mohamed","year":"2022","unstructured":"Mohamed MA, Elkhateeb WA, Daba GM. 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