{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T21:05:13Z","timestamp":1724015113920},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n<jats:title><jats:italic>Context:<\/jats:italic><\/jats:title>\n<jats:p>Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing\u2019s syndrome and adrenal crisis.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Objective:<\/jats:italic><\/jats:title>\n<jats:p>To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Design and methods:<\/jats:italic><\/jats:title>\n<jats:p>Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS\/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Results:<\/jats:italic><\/jats:title>\n<jats:p>Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC<jats:sub>0-<\/jats:sub><jats:sub>24h<\/jats:sub> within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55\u201365% and 70\u201375% for children, infants and neonates, respectively, with low cortisol levels being most prevalent.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Conclusions:<\/jats:italic><\/jats:title>\n<jats:p>Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC<jats:sub>0-<\/jats:sub><jats:sub>24h<\/jats:sub>, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0231","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T17:09:19Z","timestamp":1593796159000},"page":"357-368","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":8,"title":["Paediatric population pharmacokinetic modelling to assess hydrocortisone replacement dosing regimens in young children"],"prefix":"10.1093","volume":"183","author":[{"given":"Robin","family":"Michelet","sequence":"first","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Melin","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"},{"name":"2Graduate Research Training Program, PharMetrX, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zinnia P.","family":"Parra-Guillen","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"},{"name":"3Pharmacometrics and Systems Pharmacology, University of Navarra, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta","family":"Neumann","sequence":"additional","affiliation":[{"name":"4Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Martin","family":"Whitaker","sequence":"additional","affiliation":[{"name":"5Diurnal Limited, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viktoria","family":"Stachanow","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"},{"name":"2Graduate Research Training Program, PharMetrX, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelm","family":"Huisinga","sequence":"additional","affiliation":[{"name":"6Institute of Mathematics, Universit\u00e4t Potsdam, Potsdam, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Porter","sequence":"additional","affiliation":[{"name":"5Diurnal Limited, Cardiff, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"4Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J.","family":"Ross","sequence":"additional","affiliation":[{"name":"7University of Sheffield, Sheffield, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Kloft","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/4\/EJE-20-0231.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/4\/EJE-20-0231.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:14:45Z","timestamp":1676391285000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/4\/357\/6653762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0231","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}