부산대학교 도서관

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1365-2125.2009.03468.x Byline: Marina Braun (1), Jan-Peer Elshoff (1), Jens-Otto Andreas (1), Louise Ischen Muller (2), Rolf Horstmann (1) Keywords: drug-drug interaction; oral contraceptives; ovulation suppression; pharmacodynamics; pharmacokinetics; rotigotine transdermal patch Abstract: WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * The non-ergolinic dopamine agonist rotigotine was developed for the treatment of Parkinson's disease and restless legs syndrome as a silicone-based matrix-type transdermal system. * Dopamine 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. WHAT THIS STUDY ADDS * Concomitant administration of 3 mg (24 h).sup.-1 transdermal rotigotine has no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel. * The study results suggest that application of the transdermal rotigotine patch has no influence on contraceptive efficacy. AIMS To assess the influence of the transdermally applied dopamine agonist rotigotine on ovulation suppression by a combined oral contraceptive (0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel) in a randomized, double-blind crossover study in 40 healthy females. METHODS Treatment A consisted of the combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2 mg (24 h).sup.-1 on days 1-3, 3 mg (24 h).sup.-1 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. RESULTS Progesterone serum concentrations remained below 2 ng ml.sup.-1 in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters C.sub.max,ss and AUC(0,24 h).sub.ss at steady state were similar with or without co-administration 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): C.sub.max,ss 1.05 (0.93, 1.19), AUC(0,24 h).sub.ss 1.05 (0.9, 1.22) for ethinyloestradiol; C.sub.max,ss 1.01 (0.96, 1.06), AUC(0,24 h).sub.ss 0.98 (0.95, 1.01) for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine remained stable throughout the patch-on period (day 13). CONCLUSIONS Concomitant administration of 3 mg (24 h).sup.-1 transdermal rotigotine had no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel, suggesting that the dopamine agonist does not influence contraception efficacy. Author Affiliation: (1)Schwarz Biosciences GmbH, UCB-Group, Monheim am Rhein, Germany and (2)Parexel International, 101 Windsor Park, George, South Africa Article History: Received6 March 2009Accepted16 May 2009 Article note: Dr Marina Braun, Global Clinical Pharmacology, Global Exploratory Development, Schwarz Biosciences GmbH, UCB-Group, Alfred-Nobel-Str. 10, 40789 Monheim, Germany, Tel.: + 49 21 7348 2183, Fax: + 49 21 7348 1879, E-mail: Marina.Braun@ucb.com