{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:52:11Z","timestamp":1792068731304,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Characterizing dolutegravir penetration into the central nervous system is important for optimizing human immunodeficiency virus treatment outcomes, yet population\u2010specific pharmacokinetic data describing cerebrospinal fluid disposition and equilibration kinetics remain lacking. This study characterizes dolutegravir pharmacokinetics in plasma and cerebrospinal fluid to describe the plasma\u2010to\u2010cerebrospinal fluid equilibration rate constant and cerebrospinal fluid\u2010to\u2010plasma pseudo\u2010partition coefficient. Sparse pharmacokinetics samples were collected from 121 antiretroviral therapy\u2010experienced adults who are predominantly overweight or obese (body mass index: 32.2\u2009\u00b1\u20098.7\u2009kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ) receiving daily dolutegravir (50\u2009mg)\u2010based therapy. The model was developed using nonlinear mixed\u2010effects modeling in NONMEM. Plasma dolutegravir pharmacokinetics were best described by a one\u2010compartment model with first\u2010order absorption and elimination. The population estimate for apparent oral clearance was 1.38\u2009L\/h\/70\u2009kg. Cerebrospinal fluid data were modeled using a sequential approach with a hypothetical effect compartment linked to plasma to estimate equilibration kinetics and relative cerebrospinal fluid exposure at steady\u2010state. Key cerebrospinal fluid penetration parameters included a plasma\u2010to\u2010cerebrospinal fluid equilibration rate constant of 0.38\u2009h\n                    <jats:sup>\u22121<\/jats:sup>\n                    , corresponding to an equilibration half\u2010life of 1.82\u2009h, and a cerebrospinal fluid\u2010to\u2010plasma pseudo\u2010partition coefficient of 0.0015, indicating 0.15% cerebrospinal fluid penetration relative to plasma. Post hoc estimated area under the concentration\u2010time curve (0\u201324) demonstrated a moderate inverse correlation with body mass index (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u22120.34), indicating that dolutegravir exposure decreases with increasing body mass index. The model revealed rapid plasma\u2010to\u2010cerebrospinal fluid equilibration kinetics with low steady\u2010state cerebrospinal fluid penetration in this predominantly overweight and obese population.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70345","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:16:43Z","timestamp":1790745403000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics of Dolutegravir in Plasma and Cerebrospinal Fluid in Adults Living With HIV"],"prefix":"10.1002","volume":"15","author":[{"given":"Mohammed W.","family":"Ali","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Stellenbosch University  Cape Town South Africa"},{"name":"Department of Clinical Pharmacology and Therapeutics Gombe State University  Gombe Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Nightingale","sequence":"additional","affiliation":[{"name":"HIV Mental Health Research Unit, Department of Psychiatry and Mental Health University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Stellenbosch University  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Joska","sequence":"additional","affiliation":[{"name":"HIV Mental Health Research Unit, Department of Psychiatry and Mental Health University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-8416","authenticated-orcid":false,"given":"Alan","family":"Winston","sequence":"additional","affiliation":[{"name":"Imperial College Healthcare NHS Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saye","family":"Khoo","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-7173","authenticated-orcid":false,"given":"Joseph F.","family":"Standing","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Stellenbosch University  Cape Town South Africa"},{"name":"School of Pharmacy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1815-5150","authenticated-orcid":false,"given":"Eric H.","family":"Decloedt","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine Stellenbosch University  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-3614","authenticated-orcid":false,"given":"Ahmed A.","family":"Abulfathi","sequence":"additional","affiliation":[{"name":"Certara  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2055-6640(20)30490-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.06.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy267"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000300"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky508"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-017-2717-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06851-9"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100573"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2023.2189855"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu477"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00292-13"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz174"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.70013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(24)00209-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2013.11.054"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00215-22"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15604"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12639"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1979253358"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf178"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOPA.0000012998.04442.1f"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12052"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.4102\/sajhivmed.v23i1.1452"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaf305"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-007-9502-2"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01209-10"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw406"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e31829ed7a4"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2665"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.734122"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00507-10"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000618"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2494"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00430-23"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.13244"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz217"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.13.190"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70345","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/psp4.70345","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.70345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:18:12Z","timestamp":1792066692000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.70345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/psp4.70345"],"URL":"https:\/\/doi.org\/10.1002\/psp4.70345","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70345"}}