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We report here a Phase I, randomized, double\u2010blind, placebo\u2010controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10\u2013100\u2009mg\/kg) and multiple (75 and 100\u2009mg\/kg\/day) ascending doses of PPI\u20101011 in healthy adults. All treatment\u2010emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI\u20101011 groups, suggesting they were likely related to the oil\u2010based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100\u2009mg\/kg) and multiple\u2010dose (75 and 100\u2009mg\/kg, once daily) administration of PPI\u20101011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0\/22:6). With a once\u2010daily regimen, PPI\u20101011 administration resulted in a sustained increase of PlsEtn 16:0\/22:6 serum concentrations in healthy participants over a duration of 14\u2009days and beyond.<\/jats:p>","DOI":"10.1111\/cts.70195","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T06:08:23Z","timestamp":1741932503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["First\u2010In\u2010Human Safety, Tolerability, and Pharmacokinetics of <scp>PPI<\/scp>\u20101011, a Synthetic Plasmalogen Precursor"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-8910","authenticated-orcid":false,"given":"Tara","family":"Smith","sequence":"first","affiliation":[{"name":"Med\u2010Life Discoveries LP  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-8939","authenticated-orcid":false,"given":"Kaeli J.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Med\u2010Life Discoveries LP  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-4937","authenticated-orcid":false,"given":"Shawn A.","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Med\u2010Life Discoveries LP  Saskatoon Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01889-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1989.tb02912.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-381"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-369"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-377"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00711817"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02435984"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.10.003"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv305"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61413"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37961"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10124"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21623"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.09.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205052772786"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2009.205"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2012.02.019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02205-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2014.01.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.05.008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.06.004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14082"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00185a019"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72063"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1177\/107385840100700308","article-title":"Plasmalogens: Workhorse Lipids of Membranes in Normal and Injured Neurons and Glia","volume":"7","author":"Farooqui A. 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