{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:32:06Z","timestamp":1790109126940,"version":"4.0.1"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low\u2010dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)\/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisi\u00e8re Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK\/PD model parameters were fitted over the entire population and linked to age, weight, height and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 29 patients (age 52 [46\u201364] years, 69% female). NOR median time to peak effect on MAP was 74 [53\u201394] s. After bolus administration, MAP increased by 24% (15\u201331%). A 2\u2010comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We have developed a PK\/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target\u2010controlled infusion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16180","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T05:29:22Z","timestamp":1721712562000},"page":"2861-2869","source":"Crossref","is-referenced-by-count":7,"title":["Design of a pharmacokinetic\/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-4554","authenticated-orcid":false,"given":"Jona","family":"Joachim","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Anaesthesiology, Burn and Critical Care St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3559-4887","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Cartailler","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Anaesthesiology, Burn and Critical Care St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8204-3626","authenticated-orcid":false,"given":"Fabrice","family":"Vallee","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Anaesthesiology, Burn and Critical Care St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Lefevre","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, Burn and Critical Care St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Callebert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Service of Biochemistry and Molecular Biology St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3334-3849","authenticated-orcid":false,"given":"Etienne","family":"Gayat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Anaesthesiology, Burn and Critical Care St\u2010Louis\u2010Lariboisi\u00e8re\u2010Fernand Widal University Hospitals  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lavielle","sequence":"additional","affiliation":[{"name":"Inria &amp; CMAP, Ecole Polytechnique, CNRS Institut Polytechnique de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e31825683dc"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3182a10e26"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000270724.40897.8e"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3182472320"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2017.09.007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002483"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201806\u20101034OC"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000001880"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.2394"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.14172"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000001239"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002581"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005888"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.5208193"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.17487\/RFC5905"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010011\u20109255\u2010z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12742"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201070220\u2010w"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20102828(90)91460\u2010o"},{"key":"e_1_2_11_21_1","volume-title":"Snapshots of hemodynamics: an aid for clinical research and graduate education|SpringerLink"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12412"},{"issue":"3","key":"e_1_2_11_23_1","first-page":"340","article-title":"Evidence for alpha 1\u2010adrenergic receptor internalization in DDT1 MF\u20102 cells following exposure to agonists plus protein kinase C activators","volume":"34","author":"Cowlen MS","year":"1988","journal-title":"Mol Pharmacol"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2022.01.022"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.16180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T13:46:24Z","timestamp":1730295984000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.16180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,22]]},"references-count":23,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1111\/bcp.16180"],"URL":"https:\/\/doi.org\/10.1111\/bcp.16180","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,22]]}}}