{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T21:11:23Z","timestamp":1719263483325},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,5,26]],"date-time":"2009-05-26T00:00:00Z","timestamp":1243296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:sec><jats:label \/><jats:p> <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003The non\u2010ergolinic dopamine agonist rotigotine was developed for the treatment of Parkinson's disease and restless legs syndrome as a silicone\u2010based matrix\u2010type transdermal system.<\/jats:p><jats:p>\u2022\u2003Dopamine agonists have been recommended as initial treatment in young patients with restless legs syndrome which has a higher prevalence in females. It is therefore likely that the rotigotine transdermal patch will be administered to young women taking oral contraceptives.<\/jats:p><jats:p> <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold> <\/jats:p><jats:p>\u2022\u2003Concomitant administration of 3\u2003mg\u2003(24\u2003h)<jats:sup>\u22121<\/jats:sup> transdermal rotigotine has no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03\u2003mg ethinyloestradiol and 0.15\u2003mg levonorgestrel.<\/jats:p><jats:p>\u2022\u2003The study results suggest that application of the transdermal rotigotine patch has no influence on contraceptive efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>AIMS<\/jats:title><jats:p>To assess the influence of the transdermally applied dopamine agonist rotigotine on ovulation suppression by a combined oral contraceptive (0.03\u2003mg ethinyloestradiol and 0.15\u2003mg levonorgestrel) in a randomized, double\u2010blind crossover study in 40 healthy females.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Treatment A consisted of the combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2\u2003mg\u2003(24\u2003h)<jats:sup>\u22121<\/jats:sup> on days 1\u20133, 3\u2003mg\u2003(24\u2003h)<jats:sup>\u22121<\/jats:sup> maintenance dose thereafter). During treatment B, subjects received matching placebo patches instead of rotigotine. Pharmacodynamic parameters (progesterone, oestradiol, luteinizing hormone, and follicle stimulating hormone serum concentrations), pharmacokinetic parameters for ethinyloestradiol\/levonorgestrel and rotigotine, and safety and tolerability of the treatment were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Progesterone serum concentrations remained below 2\u2003ng\u2003ml<jats:sup>\u22121<\/jats:sup> in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters <jats:italic>C<\/jats:italic><jats:sub>max,ss<\/jats:sub> and AUC(0,24\u2003h)<jats:sub>ss<\/jats:sub> at steady state were similar with or without co\u2010administration of rotigotine for both ethinyloestradiol and levonorgestrel with geometric mean ratios close to 1 and 90% confidence intervals within the acceptance range of bioequivalence (0.8, 1.25): <jats:italic>C<\/jats:italic><jats:sub>max,ss<\/jats:sub> 1.05 (0.93, 1.19), AUC(0,24\u2003h)<jats:sub>ss<\/jats:sub> 1.05 (0.9, 1.22) for ethinyloestradiol; <jats:italic>C<\/jats:italic><jats:sub>max,ss<\/jats:sub> 1.01 (0.96, 1.06), AUC(0,24\u2003h)<jats:sub>ss<\/jats:sub> 0.98 (0.95, 1.01) for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine remained stable throughout the patch\u2010on period (day 13).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Concomitant administration of 3\u2003mg\u2003(24\u2003h)<jats:sup>\u22121<\/jats:sup> transdermal rotigotine had no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03\u2003mg ethinyloestradiol and 0.15\u2003mg levonorgestrel, suggesting that the dopamine agonist does not influence contraception efficacy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2125.2009.03468.x","type":"journal-article","created":{"date-parts":[[2009,5,25]],"date-time":"2009-05-25T09:03:26Z","timestamp":1243242206000},"page":"386-394","source":"Crossref","is-referenced-by-count":7,"title":["Influence of transdermal rotigotine on ovulation suppression by a combined oral contraceptive"],"prefix":"10.1111","volume":"68","author":[{"given":"Marina","family":"Braun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan\u2010Peer","family":"Elshoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens\u2010Otto","family":"Andreas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise Ischen","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Horstmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,9,7]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.65.2_suppl_1.S3"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252355.79284.22"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70108-4"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2007.04.010"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70112-1"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746100-00003"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200519110-00006"},{"key":"e_1_2_6_9_2","first-page":"1091","article-title":"Low drug\u2010drug interaction potential of rotigotine","volume":"45","author":"Hansen K","year":"2005","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199528030-00003"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0010-7824(79)90098-2"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200746020-00003"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199309010-00003"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2006.01.001"},{"key":"e_1_2_6_15_2","unstructured":"U.S. Food and Drug Administration.Guidance for industry: skin irritation and sensitization testing of generic transdermal drug products. 99D\u20100236 1999."},{"key":"e_1_2_6_16_2","volume-title":"Laboratory and Diagnosis","author":"Thomas L","year":"2005"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(99)70120-1"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03334.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2006.08.004"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200039040-00001"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2009.03468.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2009.03468.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:51:17Z","timestamp":1697439077000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2009.03468.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,9]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,9]]}},"alternative-id":["10.1111\/j.1365-2125.2009.03468.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2009.03468.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,9]]}}}