{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:41:35Z","timestamp":1786984895850,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To compare the pharmacokinetics (PK) of the progestin levonorgestrel for various routes of administration, an integrated population PK analysis was performed. This analysis integrated data from 10 clinical pharmacology studies and resulted in a single, comprehensive population PK model (and its applications) describing the PK of levonorgestrel and its variability for 6 levonorgestrel\u2010containing contraceptives: 3 intrauterine systems (IUSs; levonorgestrel [LNG]\u2010IUS\u00a020 [Mirena<jats:sup>\u00ae<\/jats:sup>], LNG\u2010IUS\u00a012 [Kyleena<jats:sup>\u00ae<\/jats:sup>], and LNG\u2010IUS\u00a08 [Jaydess<jats:sup>\u00ae<\/jats:sup>\/Skyla<jats:sup>\u00ae<\/jats:sup>]); 2 oral contraceptives (the progestin\u2010only pill [Microlut<jats:sup>\u00ae<\/jats:sup>\/Norgeston<jats:sup>\u00ae<\/jats:sup>] and the combined oral contraceptive [Miranova<jats:sup>\u00ae<\/jats:sup>]); and a subdermal implant (Jadelle<jats:sup>\u00ae<\/jats:sup>). The levonorgestrel\u2010containing contraceptives administered orally or as an implant act mainly via their systemic (unbound) levonorgestrel exposure, whereas levonorgestrel administered via an IUS is released directly into the uterine cavity, resulting in lower systemic levonorgestrel concentrations. The integrated population PK analysis revealed that the combined oral contraceptive led to the highest levonorgestrel exposure, followed by the progestin\u2010only pill and the implant, which led to similar levonorgestrel exposure, and the IUSs, which led to the lowest levonorgestrel exposure (in decreasing order: LNG\u2010IUS\u00a020, LNG\u2010IUS\u00a012, and LNG\u2010IUS\u00a08). The difference was even more distinct at the end of the indicated duration of use of 3\u00a0years (LNG\u2010IUS\u00a08) and 5\u00a0years (LNG\u2010IUS\u00a020 and LNG\u2010IUS\u00a012). Comparing the 3 IUSs and the implant, in vivo release rates were highest for the implant, followed by LNG\u2010IUS\u00a020, then LNG\u2010IUS\u00a012, and were lowest for LNG\u2010IUS\u00a08. This is in line with the comparison of the total levonorgestrel concentrations.<\/jats:p>","DOI":"10.1002\/jcph.1288","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T14:24:40Z","timestamp":1536762280000},"page":"1639-1654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["An Integrated Population Pharmacokinetic Analysis to Characterize Levonorgestrel Pharmacokinetics After Different Administration Routes"],"prefix":"10.1002","volume":"58","author":[{"given":"Isabel","family":"Reinecke","sequence":"first","affiliation":[{"name":"Clinical Pharmacometrics Bayer AB, Solna, Sweden, on behalf of Bayer AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics Bayer AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emir","family":"Mesic","sequence":"additional","affiliation":[{"name":"LAP&amp;P Consultants BV  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk\u2010Jan","family":"Drenth","sequence":"additional","affiliation":[{"name":"LAP&amp;P Consultants BV  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Garmann","sequence":"additional","affiliation":[{"name":"Clinical Pharmacometrics Bayer AG  Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmg004"},{"key":"e_1_2_9_3_1","unstructured":"International Federation of Gynecology & Obstetrics (FIGO) International Consortium for Emergency Contraception \u2013 Joint Statement.Mechanism of action: How do levonorgestrel\u2010only emergency contraceptive pills (LNG ECPs) prevent pregnancy?2011.http:\/\/www.figo.org\/news\/new-download-mechanism-action-how-do-levonorgestrel-only-emergency-contraceptive-pills-lng-ecps. 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Accessed May 10 2018."},{"key":"e_1_2_9_15_1","unstructured":"Bayer HealthCare Pharmaceuticals Inc.Mirena\u00aeprescribing information;2017.http:\/\/labeling.bayerhealthcare.com\/html\/products\/pi\/Mirena_PI.pdf. Accessed May 10 2018."},{"key":"e_1_2_9_16_1","unstructured":"Bayer HealthCare Pharmaceuticals.(LNG\u2010IUS 12) Kyleena\u00aesummary of product characteristics;2017.https:\/\/www.medicines.org.uk\/emc\/medicine\/33849. Accessed May 10 2018."},{"key":"e_1_2_9_17_1","unstructured":"Bayer HealthCare Pharmaceuticals Inc.Kyleena\u00aeprescribing information;2016.http:\/\/labeling.bayerhealthcare.com\/html\/products\/pi\/Kyleena_PI.pdf. Accessed May 10 2018."},{"key":"e_1_2_9_18_1","unstructured":"Bayer HealthCare Pharmaceuticals.(LNG\u2010IUS 8) Jaydess\u00aesummary of product characteristics;2017.https:\/\/www.medicines.org.uk\/emc\/medicine\/28672. 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