{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:27:39Z","timestamp":1793730459790,"version":"4.6.1"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The aim of this study was to determine the cerebrospinal fluid (CSF) to plasma concentration ratio of atogepant. Healthy adult participants (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200928) were enrolled into this phase 1, open\u2010label study and received atogepant 60\u2009mg once daily for 8\u2009days. Steady\u2010state atogepant concentrations were determined from CSF samples collected on Day 6 at 2 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) or 6 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912)\u2009h postdose, and plasma samples were collected over 24\u2009h after the Day 7 dose. Descriptive statistics for the atogepant CSF\u2010to\u2010plasma (CSF\/plasma) ratio were calculated for each time point. The safety and tolerability profiles of atogepant were evaluated by clinical assessment of adverse events, physical examinations, 12\u2010lead ECGs, laboratory tests, and vital sign measurements. The majority of adverse events were nonserious and mild in severity. Two participants discontinued the study. One due to asymptomatic moderately elevated liver enzymes and another due to mild confusional state\/insomnia. Steady\u2010state mean\u2009\u00b1\u2009SD plasma\n                    <jats:sub>total<\/jats:sub>\n                    (bound\u2009+\u2009unbound) and CSF atogepant concentrations at 2\u2009h were 652.54\u2009\u00b1\u2009385.40 and 0.49\u2009\u00b1\u20090.78\u2009ng\/mL, and at 6\u2009h were 163.14\u2009\u00b1\u200985.87 and 1.21\u2009\u00b1\u20091.14\u2009ng\/mL, respectively. The mean atogepant CSF\/plasma\n                    <jats:sub>total<\/jats:sub>\n                    concentration ratio was 0.1% at 2\u2009h and 0.7% at 6\u2009h postdose. CSF\/plasma\n                    <jats:sub>unbound<\/jats:sub>\n                    concentration ratios at 2 and 6\u2009h were 1.4% and 14.3%, respectively. Although the CNS penetration was low, considering atogepant's high affinity to CGRP receptors (Ki\u2009=\u20090.016\u2009ng\/mL) and a CIDV (capsaicin\u2010induced dermal vasodilation) EC\n                    <jats:sub>50<\/jats:sub>\n                    (half maximal effective concentration) value of 0.91\u2009ng\/mL, more research is needed to determine if atogepant acts both centrally and peripherally to prevent\/treat a migraine attack.\n                  <\/jats:p>","DOI":"10.1111\/cts.70610","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T04:20:58Z","timestamp":1779942058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cerebrospinal Fluid and Plasma Concentrations of Atogepant in Humans"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8267-9210","authenticated-orcid":false,"given":"Ramesh R.","family":"Boinpally","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2376-8878","authenticated-orcid":false,"given":"Joel M.","family":"Trugman","sequence":"additional","affiliation":[{"name":"Clinical Development AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11706-1"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13601"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00310.x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14692"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01644-8"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01481-w"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.1.3"},{"key":"e_1_2_13_9_1","volume-title":"QULIPTA (Atogepant) [Package Insert]","author":"AbbVie Inc","year":"2025"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221083544"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-025-02127-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1610"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1267"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13707"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024231226186"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/25158163231191582"},{"key":"e_1_2_13_17_1","unstructured":"European Medicines Agency \u201cAquipta Assessment Report \u201dEMA\/CHMP\/326142\/2023 2023 https:\/\/www.ema.europa.eu\/en\/documents\/assessment\u2010report\/aquipta\u2010epar\u2010public\u2010assessment\u2010report_en.pdf."},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.206458"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70560"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413476372"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01894-0"},{"issue":"1","key":"e_1_2_13_22_1","article-title":"Lasmiditan Actsspecifically on the 5\u2010HT1F Receptor in the Central Nervous System","volume":"36","author":"Kovalchin J.","year":"2016","journal-title":"Cephalalgia"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2018.01.005"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-025-03934-3"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024251346925"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1586\/ern.09.103"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01365-w"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70610","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70610","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:54:05Z","timestamp":1782104045000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/cts.70610"],"URL":"https:\/\/doi.org\/10.1111\/cts.70610","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]},"assertion":[{"value":"2026-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70610"}}