{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:33:46Z","timestamp":1770338026518,"version":"3.49.0"},"reference-count":9,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>It is known that a small fraction of <jats:italic>orally<\/jats:italic> administered norethisterone is metabolically converted to ethinylestradiol. This exploratory, open\u2010label, nonrandomized study was conducted to investigate the systemic exposure to ethinylestradiol after <jats:italic>intramuscular<\/jats:italic> administration of norethisterone enantate in comparison with the exposure to ethinylestradiol after administration of a standard combined oral contraceptive. Sixteen healthy premenopausal women received an oral contraceptive (ethinylestradiol 30\u00a0\u03bcg\/levonorgestrel 150\u00a0\u03bcg) once daily for 21 days and\u2014after a 1\u2010week washout period\u2014a single intramuscular dose of 200\u00a0mg norethisterone enantate. Blood samples to determine ethinylestradiol in serum were taken over 24 hours after the last dose of ethinylestradiol\/levonorgestrel and over 8 weeks after administration of norethisterone enantate. Oral equivalent doses of ethinylestradiol were estimated based on area under the concentration\u2013time curves. The ethinylestradiol serum concentrations observed after administration of norethisterone enantate were relatively low: The mean maximum concentration was only 32% of the maximum observed after ethinylestradiol\/levonorgestrel (90%\u00a0confidence interval, 22.5%\u201344.7%). The maximum oral equivalent dose of ethinylestradiol was markedly lower than 30\u00a0\u03bcg ethinylestradiol per day (20.3\u00a0\u03bcg\/day; 90%\u00a0confidence interval, 14.8\u201328.0\u00a0\u03bcg\/day). The same applied to the average oral equivalent dose of ethinylestradiol for the 8\u2010week postdose interval (4.41\u00a0\u03bcg\/day; 90%\u00a0confidence interval, 3.57\u20135.46\u00a0\u03bcg\/day). To conclude, the study results indicate that metabolic conversion of norethisterone to ethinylestradiol also occurs after intramuscular administration of 200\u00a0mg norethisterone enantate, but is associated with a lower exposure to ethinylestradiol than the use of a combined oral contraceptive containing 30\u00a0\u03bcg ethinylestradiol (plus 150\u00a0\u03bcg levonorgestrel).<\/jats:p>","DOI":"10.1002\/jcph.1079","type":"journal-article","created":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T15:52:49Z","timestamp":1520610769000},"page":"781-789","source":"Crossref","is-referenced-by-count":10,"title":["In Vivo Formation of Ethinylestradiol After Intramuscular Administration of Norethisterone Enantate"],"prefix":"10.1002","volume":"58","author":[{"given":"Christian","family":"Friedrich","sequence":"first","affiliation":[{"name":"Bayer AG  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Berse","sequence":"additional","affiliation":[{"name":"CRS Clinical Research Services Berlin GmbH  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Klein","sequence":"additional","affiliation":[{"name":"Bayer AG  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Rohde","sequence":"additional","affiliation":[{"name":"Bayer AG  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"H\u00f6chel","sequence":"additional","affiliation":[{"name":"Bayer AG  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(90)90093-B"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(90)90342-I"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5122(94)00894-D"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(97)00174-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0044"},{"key":"e_1_2_8_7_1","unstructured":"European Medicines Agency.Guideline on bioanalytical method validation.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2011\/08\/WC500109686.pdf. Accessed November 20 2017."},{"key":"e_1_2_8_8_1","unstructured":"US Food and Drug Administration.Guidance for industry: Bioanalytical method validation.http:\/\/www.fda.gov\/downloads\/Drugs\/Guidances\/ucm070107.pdf. Accessed November 20 2017."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(81)90065-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1008"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1079","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T23:20:20Z","timestamp":1694301620000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,9]]},"references-count":9,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/jcph.1079"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1079","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,9]]}}}