{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:15:22Z","timestamp":1791976522747,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T00:00:00Z","timestamp":1618617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T00:00:00Z","timestamp":1618617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Pharmacokinet"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1007\/s40262-021-01011-3","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T22:03:05Z","timestamp":1618610585000},"page":"1217-1226","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Population Pharmacokinetics and Pharmacodynamics of Once-Daily Growth Hormone Norditropin\u00ae in Children and Adults"],"prefix":"10.1007","volume":"60","clinical-trial-number":[{"clinical-trial-number":"nct01973244","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00936403","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01706783","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Theodoros","family":"Papathanasiou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Agers\u00f8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte Bentz","family":"Damholt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"H\u00f8jby Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0965-9333","authenticated-orcid":false,"given":"Rasmus Juul","family":"Kildemoes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,17]]},"reference":[{"issue":"5","key":"1011_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1111\/j.1365-2265.1992.tb02347.x","volume":"37","author":"RC Cuneo","year":"1992","unstructured":"Cuneo RC, Salomon F, McGauley GA, Sonksen PH. The growth hormone deficiency syndrome in adults. Clin Endocrinol (Oxf). 1992;37(5):387\u201397.","journal-title":"Clin Endocrinol (Oxf)"},{"key":"1011_CR2","doi-asserted-by":"crossref","unstructured":"Attanasio AF, Lamberts SW, Matranga AM, Birkett MA, Bates PC, Valk NK, et al. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group. J Clin Endocrinol Metab. 1997;82(1):82\u20138.","DOI":"10.1210\/jc.82.1.82"},{"issue":"6","key":"1011_CR3","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1159\/000452150","volume":"86","author":"A Grimberg","year":"2016","unstructured":"Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361\u201397.","journal-title":"Horm Res Paediatr."},{"key":"1011_CR4","doi-asserted-by":"crossref","unstructured":"Raben MS. Growth hormone. 2. Clinical use of human growth hormone. N Engl J Med. 1962;266:82\u20136.","DOI":"10.1056\/NEJM196201112660207"},{"issue":"8649","key":"1011_CR5","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/S0140-6736(89)92328-3","volume":"1","author":"JO Jorgensen","year":"1989","unstructured":"Jorgensen JO, Pedersen SA, Thuesen L, Jorgensen J, Ingemann-Hansen T, Skakkebaek NE, et al. Beneficial effects of growth hormone treatment in GH-deficient adults. Lancet. 1989;1(8649):1221\u20135.","journal-title":"Lancet"},{"issue":"26","key":"1011_CR6","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1056\/NEJM198912283212605","volume":"321","author":"F Salomon","year":"1989","unstructured":"Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989;321(26):1797\u2013803.","journal-title":"N Engl J Med"},{"issue":"5","key":"1011_CR7","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1530\/EJE-12-1083","volume":"168","author":"M Elbornsson","year":"2013","unstructured":"Elbornsson M, Gotherstrom G, Bosaeus I, Bengtsson BA, Johannsson G, Svensson J. Fifteen years of GH replacement improves body composition and cardiovascular risk factors. Eur J Endocrinol. 2013;168(5):745\u201353.","journal-title":"Eur J Endocrinol"},{"issue":"6","key":"1011_CR8","first-page":"717","volume":"19","author":"A Giustina","year":"1998","unstructured":"Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19(6):717\u201397.","journal-title":"Endocr Rev"},{"issue":"26","key":"1011_CR9","doi-asserted-by":"publisher","first-page":"2551","DOI":"10.1056\/NEJMra1817346","volume":"380","author":"S Melmed","year":"2019","unstructured":"Melmed S. Pathogenesis and diagnosis of growth hormone deficiency in adults. N Engl J Med. 2019;380(26):2551\u201362.","journal-title":"N Engl J Med"},{"issue":"6","key":"1011_CR10","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1210\/jcem-70-6-1616","volume":"70","author":"JO Jorgensen","year":"1990","unstructured":"Jorgensen JO, Moller N, Lauritzen T, Christiansen JS. Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor-I and metabolic indices. J Clin Endocrinol Metab. 1990;70(6):1616\u201323.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1011_CR11","first-page":"1222","volume":"86","author":"T Laursen","year":"2001","unstructured":"Laursen T, Gravholt CH, Heickendorff L, Drustrup J, Kappelgaard AM, J\u00f8rgensen JOL, et al. Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults. J Clin Endocrinol Metab. 2001;86(3):1222\u20138.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1011_CR12","first-page":"155","volume":"20","author":"S Wacharasindhu","year":"2002","unstructured":"Wacharasindhu S, Aroonparkmongkol S, Srivuthana S. Measurement of IGF-1, IGFBP-3 and free IGF-1 levels by ELISA in growth hormone (GH) deficient children before and after GH replacement. Asian Pac J Allergy Immunol. 2002;20(3):155\u201360.","journal-title":"Asian Pac J Allergy Immunol"},{"issue":"11","key":"1011_CR13","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.4158\/GL-2019-0405","volume":"25","author":"KCJ Yuen","year":"2019","unstructured":"Yuen KCJ, Biller BMK, Radovick S, Carmichael JD, Jasim S, Pantalone KM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients transitioning from pediatric to adult care. Endocr Pract. 2019;25(11):1191\u2013232.","journal-title":"Endocr Pract."},{"issue":"Suppl. 4","key":"1011_CR14","first-page":"77","volume":"33","author":"JO Jorgensen","year":"1990","unstructured":"Jorgensen JO, Moller J, Moller N, Lauritzen T, Christiansen JS. Pharmacological aspects of growth hormone replacement therapy: route, frequency and timing of administration. Horm Res. 1990;33(Suppl. 4):77\u201382.","journal-title":"Horm Res"},{"issue":"5","key":"1011_CR15","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1210\/jcem-72-5-1148","volume":"72","author":"GL Kearns","year":"1991","unstructured":"Kearns GL, Kemp SF, Frindik JP. Single and multiple dose pharmacokinetics of methionyl growth hormone in children with idiopathic growth hormone deficiency. J Clin Endocrinol Metab. 1991;72(5):1148\u201356.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1011_CR16","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.1210\/jc.2008-1897","volume":"94","author":"EC Walvoord","year":"2009","unstructured":"Walvoord EC, de la Pe\u00f1a A, Park S, Silverman BL, Cuttler L, Rose SR, et al. Inhaled growth hormone (GH) compared with subcutaneous GH in children with GH deficiency: pharmacokinetics, pharmacodynamics, and safety. J Clin Endocrinol Metab. 2009;94(6):2052\u20139.","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1011_CR17","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1530\/EJE-07-0057","volume":"156","author":"A Keller","year":"2007","unstructured":"Keller A, Wu Z, Kratzsch J, Keller E, Blum WF, Kniess A, et al. Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration. Eur J Endocrinol. 2007;156(6):647\u201353.","journal-title":"Eur J Endocrinol"},{"key":"1011_CR18","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1210\/jc.2006-0514","volume":"91","author":"M Bidlingmaier","year":"2006","unstructured":"Bidlingmaier M, Kim J, Savoy C, Kim MO, Ebrecht N, Motte S, et al. Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency. J Clin Endocrinol Metab. 2006;91:2926\u201330.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1011_CR19","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1111\/cen.13409","volume":"87","author":"T Battelino","year":"2017","unstructured":"Battelino T, Rasmussen MH, De Schepper J, Zuckerman-Levin N, Gucev Z, Savendahl L. Somapacitan, a once-weekly reversible albumin-binding GH derivative, in children with GH deficiency: a randomized dose-escalation trial. Clin Endocrinol (Oxf). 2017;87(4):350\u20138.","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"3","key":"1011_CR20","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1530\/EJE-11-0536","volume":"165","author":"J de Schepper","year":"2011","unstructured":"de Schepper J, Rasmussen MH, Gucev Z, Eliakim A, Battelino T. Long-acting pegylated human GH in children with GH deficiency: a single-dose, dose-escalation trial investigating safety, tolerability, pharmacokinetics and pharmacodynamics. Eur J Endocrinol. 2011;165(3):401\u20139.","journal-title":"Eur J Endocrinol"},{"issue":"3","key":"1011_CR21","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1210\/jc.2015-1991","volume":"101","author":"MH Rasmussen","year":"2016","unstructured":"Rasmussen MH, Janukonyte J, Klose M, Marina D, Tanvig M, Nielsen LF, et al. Reversible albumin-binding GH possesses a potential once-weekly treatment profile in adult growth hormone deficiency. J Clin Endocrinol Metab. 2016;101(3):988\u201398.","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"1011_CR22","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1159\/000470842","volume":"87","author":"DM Fisher","year":"2017","unstructured":"Fisher DM, Rosenfeld RG, Jaron-Mendelson M, Amitzi L, Koren R, Hart G. Pharmacokinetic and pharmacodynamic modeling of MOD-4023, a long-acting human growth hormone, in growth hormone deficiency children. Horm Res Paediatr. 2017;87(5):324\u201332.","journal-title":"Horm Res Paediatr."},{"issue":"1","key":"1011_CR23","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s40262-018-0662-5","volume":"58","author":"RV Juul","year":"2019","unstructured":"Juul RV, Rasmussen MH, Agerso H, Overgaard RV. Pharmacokinetics and pharmacodynamics of once-weekly somapacitan in children and adults: supporting dosing rationales with a model-based analysis of three phase I trials. Clin Pharmacokinet. 2019;58(1):63\u201375.","journal-title":"Clin Pharmacokinet"},{"issue":"5","key":"1011_CR24","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1210\/jc.2013-3059","volume":"99","author":"M Bidlingmaier","year":"2014","unstructured":"Bidlingmaier M, Friedrich N, Emeny RT, Spranger J, Wolthers OD, Roswall J, et al. Reference intervals for insulin-like growth factor-1 (IGF-I) from birth to senescence: results from a multicenter study using a new automated chemiluminescence IGF-I immunoassay conforming to recent international recommendations. J Clin Endocrinol Metab. 2014;99(5):1712\u201321.","journal-title":"J Clin Endocrinol Metab"},{"issue":"3","key":"1011_CR25","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1210\/jcem-68-3-535","volume":"68","author":"AC Faria","year":"1989","unstructured":"Faria AC, Veldhuis JD, Thorner MO, Vance ML. Half-time of endogenous growth hormone (GH) disappearance in normal man after stimulation of GH secretion by GH-releasing hormone and suppression with somatostatin. J Clin Endocrinol Metab. 1989;68(3):535\u201341.","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"1011_CR26","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1111\/j.1365-2265.1989.tb00444.x","volume":"30","author":"PC Hindmarsh","year":"1989","unstructured":"Hindmarsh PC, Matthews DR, Brain CE, Pringle PJ, di Silvio L, Kurtz AB, et al. The half-life of exogenous growth hormone after suppression of endogenous growth hormone secretion with somatostatin. Clin Endocrinol (Oxf). 1989;30(4):443\u201350.","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"1","key":"1011_CR27","first-page":"45","volume":"47","author":"ICH harmonized tripartite guideline","year":"2001","unstructured":"ICH harmonized tripartite guideline. guideline for good clinical practice. J Postgrad Med. 2001;47(1):45\u201350.","journal-title":"J Postgrad Med"},{"issue":"1","key":"1011_CR28","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3917\/jib.151.0124","volume":"15","author":"World Medical Association Declaration of Helsinki","year":"2004","unstructured":"World Medical Association Declaration of Helsinki. ethical principles for medical research involving human subjects. J Int Bioethique. 2004;15(1):124\u20139.","journal-title":"J Int Bioethique."}],"container-title":["Clinical Pharmacokinetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01011-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40262-021-01011-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40262-021-01011-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:40:59Z","timestamp":1630694459000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40262-021-01011-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,17]]},"references-count":28,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["1011"],"URL":"https:\/\/doi.org\/10.1007\/s40262-021-01011-3","relation":{},"ISSN":["0312-5963","1179-1926"],"issn-type":[{"value":"0312-5963","type":"print"},{"value":"1179-1926","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,17]]},"assertion":[{"value":"28 February 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Funding for this study was provided by Novo Nordisk A\/S.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Theodoros Papathanasiou and Birgitte Bentz Damholt were employees\/shareholders of Novo Nordisk A\/S at the time of writing. Henrik Agers\u00f8, Michael H\u00f8jby Rasmussen and Rasmus Juul Kildemoes are employees\/shareholders of Novo Nordisk A\/S.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest\/Competing Interests"}},{"value":"All trials were approved from the local and national ethics committees and were conducted in accordance with the International Conference on Harmonisation guidelines for Good Clinical Practice [\n                      \n                      ] and the Declaration of Helsinki [\n                      \n                      ]. For children with growth hormone deficiency, parent or guardian signed informed consent was required before the initiation of any trial activity.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The datasets generated during and\/or analysed during the current study are not publicly available, but are available from the corresponding author on reasonable request.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of Data and Material"}},{"value":"Not applicable.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by TP and RJK. The first draft of the manuscript was written by TP and RJK, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 Contributions"}}]}}