{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:43:20Z","timestamp":1792197800287,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Guidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24\u2009h area under the concentration\u2010time curve over first\u2010order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Models were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction\u2010based diagnostics, then by simulation\u2010based diagnostics and a posteriori analyses only if deemed satisfactory; model\u2010informed vancomycin exposure was also compared with reference first\u2010order pharmacokinetic equations. The best\u2010performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias \u2264 \u00b1\u200915% and imprecision  30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et\u00a0al. and Mehrotra et\u00a0al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.4623","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T04:05:26Z","timestamp":1731643526000},"page":"907-919","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["External evaluation of neonatal vancomycin population pharmacokinetic models: Moving from first\u2010order equations to Bayesian\u2010guided therapeutic monitoring"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4218-3260","authenticated-orcid":false,"given":"Mathieu","family":"Blouin","sequence":"first","affiliation":[{"name":"STP<sup>2<\/sup> Laboratory, Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-6116","authenticated-orcid":false,"given":"Marie\u2010\u00c9laine","family":"M\u00e9tras","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Department of Pharmacy CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3477-9414","authenticated-orcid":false,"given":"Marie\u2010H\u00e9l\u00e8ne","family":"Dub\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pharmacy CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"},{"name":"Research Center CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3843-6913","authenticated-orcid":false,"given":"Marie\u2010Christine","family":"Boulanger","sequence":"additional","affiliation":[{"name":"Department of Pharmacy CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"},{"name":"Research Center CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-1345","authenticated-orcid":false,"given":"Karine","family":"Cloutier","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Universit\u00e9 Laval  Quebec City Quebec Canada"},{"name":"Department of Pharmacy CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"},{"name":"Research Center CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4314-5368","authenticated-orcid":false,"given":"Mehdi","family":"El Hassani","sequence":"additional","affiliation":[{"name":"STP<sup>2<\/sup> Laboratory, Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0447-7668","authenticated-orcid":false,"given":"Aysenur","family":"Yaliniz","sequence":"additional","affiliation":[{"name":"STP<sup>2<\/sup> Laboratory, Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7120-9408","authenticated-orcid":false,"given":"Isabelle","family":"Viel\u2010Th\u00e9riault","sequence":"additional","affiliation":[{"name":"Department of Pediatrics CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9303-8862","authenticated-orcid":false,"given":"Am\u00e9lie","family":"Marsot","sequence":"additional","affiliation":[{"name":"STP<sup>2<\/sup> Laboratory, Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Faculty of Pharmacy Universit\u00e9 de Montr\u00e9al  Montreal Quebec Canada"},{"name":"Research Center CHU Sainte\u2010Justine  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/491709"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp080434"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq146"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.05.016"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa036"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03261932"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00937-4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596390-000000000-00000"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.120"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03736.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-021-00489-8"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31806db3f5"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00853-19"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1197-y"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01370-09"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-13-59"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.03.045"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.623907"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2007.12.002"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-015-1699-x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1093171"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010898"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-018-2454-0"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2865"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104278"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03620-14"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky525"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/fn.81.3.f221"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.2196\/29458"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01899-21"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2020.10.016"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.4.1159-1167.2004"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.634686"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00603"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.2012.01029.x"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-020-00302-7"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2010.196402"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02523-20"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.5414\/CP202827"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01647-17"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2012-302765"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01185-4"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-024-01353-8"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01653-13"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13210"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/32065"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01233-7"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196721"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.43146"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.4623","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:04:59Z","timestamp":1761059099000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.4623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,15]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/phar.4623"],"URL":"https:\/\/doi.org\/10.1002\/phar.4623","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,15]]},"assertion":[{"value":"2024-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}