{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:25:47Z","timestamp":1785209147550,"version":"3.55.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Patients with congenital adrenal hyperplasia (CAH) require lifelong replacement therapy with glucocorticoids. Optimizing hydrocortisone therapy is challenging, since there are no established cortisol concentration targets other than the cortisol circadian rhythm profile. 17-hydroxyprogesterone (17-OHP) concentrations are elevated in these patients and commonly used to monitor therapy. This study aimed to characterize the pharmacokinetics\/pharmacodynamics (PK\/PD) of cortisol using 17-OHP as a biomarker in pediatric patients with CAH and to assess different hydrocortisone dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cortisol and 17-OHP concentrations from 30 CAH patients (7\u201317 years of age) receiving standard hydrocortisone replacement therapy (5\u201320 mg) twice (n\u2005=\u200517) or 3 times (n\u2005=\u200513) daily were used to develop a PK\/PD model. Sequentially, simulated cortisol concentrations for clinically relevant 3- and 4-times daily dosing regimens were compared with cortisol and 17-OHP target ranges and to concentrations in healthy children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cortisol concentration-time profiles were accurately described by a 2-compartment model with first-order absorption and expected high bioavailability (82.6%). A time-delayed model with cortisol-mediated inhibition of 17-OHP synthesis accurately described 17-OHP concentrations. The cortisol concentration inhibiting 50% of 17-OHP synthesis was 48.6 nmol\/L. A 4-times-daily dosing better attained the target ranges and mimicked the cortisol concentrations throughout the 24-hour period than 3-times-daily.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A PK\/PD model following hydrocortisone administration has been established. An improved dosing regimen of 38% at 06:00, 22% at 12:00, 17% at 18:00, and 22% at 24:00 of the daily hydrocortisone dose was suggested. The 4-times-daily dosing regimen was superior, avoiding subtherapeutic cortisol concentrations and better resembling the circadian rhythm of cortisol.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa071","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T02:43:17Z","timestamp":1581561797000},"page":"e1729-e1740","source":"Crossref","is-referenced-by-count":27,"title":["Pharmacokinetic\/Pharmacodynamic Evaluation of Hydrocortisone Therapy in Pediatric Patients with Congenital Adrenal Hyperplasia"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3561-7097","authenticated-orcid":false,"given":"Johanna","family":"Melin","sequence":"first","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"},{"name":"Graduate Research Training program PharMetrX, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1503-2710","authenticated-orcid":false,"given":"Zinnia P","family":"Parra-Guillen","sequence":"additional","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"},{"name":"Pharmacometrics and Systems Pharmacology Group, Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-607X","authenticated-orcid":false,"given":"Robin","family":"Michelet","sequence":"additional","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi","family":"Truong","sequence":"additional","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5249-3914","authenticated-orcid":false,"given":"Wilhelm","family":"Huisinga","sequence":"additional","affiliation":[{"name":"Institute of Mathematics, Universit\u00e4t Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-6525","authenticated-orcid":false,"given":"Niklas","family":"Hartung","sequence":"additional","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"},{"name":"Institute of Mathematics, Universit\u00e4t Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-8518","authenticated-orcid":false,"given":"Peter","family":"Hindmarsh","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group, UCL Institute of Child Health, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9344-8514","authenticated-orcid":false,"given":"Charlotte","family":"Kloft","sequence":"additional","affiliation":[{"name":"Dept. of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"issue":"3","key":"2020081015170293300_CIT0001","first-page":"245","article-title":"Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency","volume":"21","author":"Speiser","year":"2000","journal-title":"Endocr Rev."},{"issue":"3","key":"2020081015170293300_CIT0002","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1111\/j.1365-2265.2004.02106.x","article-title":"Weight-related dosing, timing and monitoring hydrocortisone replacement therapy in patients with adrenal 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