Influence of transdermal rotigotine on ovulation suppression by a combined oral contraceptive.
OBJECTIVE
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)(-1) on days 1-3, 3 mg (24 h)(-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(-1) in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters C(max,ss) and AUC(0,24 h)(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(max,ss) 1.05 (0.93, 1.19), AUC(0,24 h)(ss) 1.05 (0.9, 1.22) for ethinyloestradiol; C(max,ss) 1.01 (0.96, 1.06), AUC(0,24 h)(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)(-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.
Braun
Marina
M
Schwarz Biosciences GmbH, UCB-Group, Monheim am Rhein, Germany. Marina.Braun@ucb.com
Elshoff
Jan-Peer
JP
Andreas
Jens-Otto
JO
Müller
Louise Ischen
LI
Horstmann
Rolf
R
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000493:pharmacokinetics; D007986:Luteinizing Hormone / Q000097:blood; D034445:Ovulation Inhibition / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D013876:Thiophenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D018491:Dopamine Agonists; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D016912:Levonorgestrel; C047508:rotigotine; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone