{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:29:55Z","timestamp":1789752595321,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To characterize cabotegravir population pharmacokinetics using data from phase 1, 2 and 3 studies and evaluate the association of intrinsic and extrinsic factors with pharmacokinetic variability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Analyses were implemented in NONMEM and R. Concentrations below the quantitation limit were modelled with likelihood\u2010based approaches. Covariate relationships were evaluated using forward addition (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.01) and backward elimination (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.001) approaches. The impact of each covariate on trough and peak concentrations was evaluated through simulations. External validation was performed using prediction\u2010corrected visual predictive checks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The model\u2010building dataset included 23\u2009926 plasma concentrations from 1647 adult HIV\u20101\u2010infected (72%) and uninfected (28%) subjects in 16 studies at seven dose levels (oral 10\u201060\u2009mg, long\u2010acting [LA] intramuscular injection 200\u2010800\u2009mg). A two\u2010compartment model with first\u2010order oral and LA absorption and elimination adequately described the data. Clearances and volumes were scaled to body weight. Estimated relative bioavailability of oral to LA was 75.6%. Race and age were not significant covariates. LA absorption rate constant (KA\n                      <jats:sub>LA<\/jats:sub>\n                      ) was 50.9% lower in females and 47.8% higher if the LA dose was given as two split injections. KA\n                      <jats:sub>LA<\/jats:sub>\n                      decreased with increasing BMI and decreasing needle length. Clearance was 17.4% higher in current smokers. The impact of any covariate was \u226432% on trough and peak concentrations following LA administration. The final model adequately predicted 5097 plasma concentrations from 647 subjects who were not included in the model\u2010building dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A cabotegravir population pharmacokinetic model was developed that can be used to inform dosing strategies and future study design. No dose adjustment based on subject covariates is recommended.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15439","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T08:46:05Z","timestamp":1655109965000},"page":"4607-4622","source":"Crossref","is-referenced-by-count":56,"title":["Population pharmacokinetics of cabotegravir following administration of oral tablet and long\u2010acting intramuscular injection in adult HIV\u20101\u2010infected and uninfected subjects"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8010-9898","authenticated-orcid":false,"given":"Kelong","family":"Han","sequence":"first","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Baker","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lovern","sequence":"additional","affiliation":[{"name":"Certara Consulting Services  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prokash","family":"Paul","sequence":"additional","affiliation":[{"name":"Certara Consulting Services  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Janssen Pharmaceuticals  Raritan NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parul","family":"Patel","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy P.","family":"Moore","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara S.","family":"Seal","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy G.","family":"Cutrell","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald D.","family":"D'Amico","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Benn","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael J.","family":"Landovitz","sequence":"additional","affiliation":[{"name":"UCLA Center for Clinical AIDS Research &amp; Education University of California  Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Marzinke","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Spreen","sequence":"additional","affiliation":[{"name":"ViiV Healthcare  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Ford","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1310\/hct1405-192"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000301"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000365"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00152-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31917-7"},{"key":"e_1_2_11_8_1","unstructured":"OrkinC Arast\u00e9hK Hern\u00e1ndez\u2010MoraMG et al.Long\u2010acting cabotegravir + rilpivirine for HIV maintenance: FLAIR week 48 results. 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