{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:34:19Z","timestamp":1791653659541,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T00:00:00Z","timestamp":1552348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Nilotinib is a broad\u2010based tyrosine kinase inhibitor with the highest affinity to inhibit Abelson (c\u2010Abl) and discoidin domain receptors (\n                    <jats:styled-content style=\"fixed-case\">DDR<\/jats:styled-content>\n                    1\/2). Preclinical evidence indicates that Nilotinib reduces the level of brain alpha\u2010synuclein and attenuates inflammation in models of Parkinson's disease (\n                    <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                    ). We previously showed that Nilotinib penetrates the blood\u2010brain barrier (\n                    <jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>\n                    ) and potentially improves clinical outcomes in individuals with\n                    <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                    and dementia with Lewy bodies (\n                    <jats:styled-content style=\"fixed-case\">DLB<\/jats:styled-content>\n                    ). We performed a physiologically based population pharmacokinetic\/pharmacodynamic (pop\n                    <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                    ) study to determine the effects of Nilotinib in a cohort of 75\n                    <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\n                    participants. Participants were randomized (1:1:1:1:1) into five groups (n\u00a0=\u00a015) and received open\u2010label random single dose (\n                    <jats:styled-content style=\"fixed-case\">RSD<\/jats:styled-content>\n                    ) 150:200:300:400\u00a0mg Nilotinib vs placebo. Plasma and cerebrospinal fluid (\n                    <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\n                    ) were collected at 1, 2, 3, and 4\u00a0hours after Nilotinib administration. The results show that Nilotinib enters the brain in a dose\u2010independent manner and 200\u00a0mg Nilotinib increases the level of 3,4\u2010Dihydroxyphenylacetic acid (\n                    <jats:styled-content style=\"fixed-case\">DOPAC<\/jats:styled-content>\n                    ) and homovanillic acid (\n                    <jats:styled-content style=\"fixed-case\">HVA<\/jats:styled-content>\n                    ), suggesting alteration to dopamine metabolism. Nilotinib significantly reduces plasma total alpha\u2010synuclein and appears to reduce\n                    <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\n                    oligomeric: total alpha\u2010synuclein ratio. Furthermore, Nilotinib significantly increases the\n                    <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>\n                    level of triggering receptors on myeloid cells (\n                    <jats:styled-content style=\"fixed-case\">TREM<\/jats:styled-content>\n                    )\u20102, suggesting an anti\u2010inflammatory effect. Taken together, 200\u00a0mg Nilotinib appears to be an optimal single dose that concurrently reduces inflammation and engages surrogate disease biomarkers, including dopamine metabolism and alpha\u2010synuclein.\n                  <\/jats:p>","DOI":"10.1002\/prp2.470","type":"journal-article","created":{"date-parts":[[2019,3,12]],"date-time":"2019-03-12T04:50:36Z","timestamp":1552366236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Fernando L.","family":"Pagan","sequence":"first","affiliation":[{"name":"Translational Neurotherapeutics Program Laboratory for Dementia and Parkinsonism Department of Neurology Georgetown University Medical Center  Washington District of Columbia"},{"name":"Movement Disorders Clinic Department of Neurology MedStar 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