{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:54:33Z","timestamp":1791536073864,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,1]]},"abstract":"<jats:sec>\n<jats:title>Context<\/jats:title>\n<jats:p>Prenatal dexamethasone therapy is used in female foetuses with congenital adrenal hyperplasia to suppress androgen excess and prevent virilisation of the external genitalia. The traditional dexamethasone dose of 20 \u00b5g\/kg\/day has been used since decades without examination in clinical trials and is thus still considered experimental.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>As the traditional dexamethasone dose potentially causes adverse effects in treated mothers and foetuses, we aimed to provide a rationale of a reduced dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on a pharmacokinetics-based modelling and simulation framework.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Based on a published dexamethasone dataset, a nonlinear mixed-effects model was developed describing maternal dexamethasone pharmacokinetics. In stochastic simulations (<jats:italic>n<\/jats:italic>\u2009= 1000), a typical pregnant population (<jats:italic>n<\/jats:italic>\u2009= 124) was split into two dosing arms receiving either the traditional 20 \u00b5g\/kg\/day dexamethasone dose or reduced doses between 5 and 10 \u00b5g\/kg\/day. Target maternal dexamethasone concentrations, identified from the literature, served as a threshold to be exceeded by 90% of mothers at a steady state to ensure foetal hypothalamic-pituitary-adrenal axis suppression.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A two-compartment dexamethasone pharmacokinetic model was developed and subsequently evaluated to be fit for purpose. The simulations, including a sensitivity analysis regarding the assumed foetal:maternal dexamethasone concentration ratio, resulted in 7.5 \u00b5g\/kg\/day to be the minimum effective dose and thus our suggested dose.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We conclude that the traditional dexamethasone dose is three-fold higher than needed, possibly causing harm in treated foetuses and mothers. The clinical relevance and appropriateness of our recommended dose should be tested in a prospective clinical trial.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0395","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T17:44:56Z","timestamp":1625593496000},"page":"365-374","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":13,"title":["Rationale of a lower dexamethasone dose in prenatal congenital adrenal hyperplasia therapy based on pharmacokinetic modelling"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-4623","authenticated-orcid":true,"given":"Viktoria","family":"Stachanow","sequence":"first","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":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Neumann","sequence":"additional","affiliation":[{"name":"3Institute for Experimental Paediatric Endocrinology, Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"3Institute for Experimental Paediatric Endocrinology, Charit\u00e9-Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Fuhr","sequence":"additional","affiliation":[{"name":"4Department I of Pharmacology, Center for Pharmacology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Huisinga","sequence":"additional","affiliation":[{"name":"5Institute of Mathematics, Universit\u00e4t Potsdam, Golm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-607X","authenticated-orcid":true,"given":"Robin","family":"Michelet","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"6Medizinische Klinik und Poliklinik IV, Klinikum der Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Kloft","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/3\/EJE-21-0395.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/3\/EJE-21-0395.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:43Z","timestamp":1676391403000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/3\/365\/6654468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0395","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,1]]}}}