{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:17:10Z","timestamp":1780049830223,"version":"3.53.1"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01HD084461"],"award-info":[{"award-number":["R01HD084461"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR000445"],"award-info":[{"award-number":["UL1 TR000445"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01\u2010GM124109"],"award-info":[{"award-number":["R01\u2010GM124109"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Our objectives were to perform a population pharmacokinetic analysis of dexmedetomidine in children using remnant specimens and electronic health records (EHRs) and explore the impact of patient's characteristics and pharmacogenetics on dexmedetomidine clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dexmedetomidine dosing and patient data were gathered from EHRs and combined with opportunistically sampled remnant specimens. Population pharmacokinetic models were developed using nonlinear mixed\u2010effects modelling. Stage 1 developed a model without genotype variables; Stage 2 added pharmacogenetic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our final study population included 354 post\u2010cardiac surgery patients aged 0\u201322\u2009years (median 16\u2009mo). The data were best described with a 2\u2010compartment model with allometric scaling for weight and Hill maturation function for age. Population parameter estimates and 95% confidence intervals were 27.3\u00a0L\/h (24.0\u201331.1\u00a0L\/h) for total clearance, 161\u2009L (139\u2013187\u2009L) for central compartment volume of distribution, 26.0\u00a0L\/h (22.5\u201330.0\u00a0L\/h) for intercompartmental clearance and 7903\u2009L (5617\u201311\u2009119\u2009L) for peripheral compartment volume of distribution. The estimate for postmenstrual age when 50% of adult clearance is achieved was 42.0\u00a0weeks (41.5\u201342.5\u00a0weeks) and the Hill coefficient estimate was 7.04 (6.99\u20137.08). Genotype was not statistically or clinically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates the use of real\u2010world EHR data and remnant specimens to perform a population pharmacokinetic analysis and investigate covariate effects in a large paediatric population. Weight and age were important predictors of clearance. We did not find evidence for pharmacogenetic effects of\n                      <jats:italic>UGT1A4<\/jats:italic>\n                      or\n                      <jats:italic>UGT2B10<\/jats:italic>\n                      genotype or\n                      <jats:italic>CYP2A6<\/jats:italic>\n                      risk score.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15194","type":"journal-article","created":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T23:04:37Z","timestamp":1640559877000},"page":"2885-2898","source":"Crossref","is-referenced-by-count":9,"title":["Population pharmacokinetic analysis of dexmedetomidine in children using real\u2010world data from electronic health records and remnant specimens"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7079-9151","authenticated-orcid":false,"given":"Nathan T.","family":"James","sequence":"first","affiliation":[{"name":"Department of Biostatistics 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