title: Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial.
abstract: BACKGROUND
  This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg.
  
  
  METHODS
  A Phase 1, open-label, single-center study in 36 healthy women was conducted over three cycles with a randomized crossover design. After a run-in cycle of 21 days on and 7 days off with AG200-15, participants were randomized to receive one of two treatments: a 21/7-day cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial is registered on ClinicalTrials.gov under the identifier NCT01243580.
  
  
  RESULTS
  During the third week of AG200-15 use, mean (±standard deviation) maximum serum concentration (C(max)), area under the curve(0-168 h) and steady-state concentration (C(ss48-168 h)) for EE were 51.3 ± 17.3 pg/mL, 6.26 ± 2.46 ng h/mL and 35.7 ± 14.5 pg/mL, respectively; for LNG, the corresponding values were 2400 ± 1140 pg/mL, 317 ± 159 ng h/mL and 1847 ± 930 pg/mL, respectively. The AG200-15 EE C(max) was approximately 60% lower and the EE C(ss) was 15%-20% lower than those obtained with the COC. The calculated daily dose of AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs; >10%) in the AG200-15 group were headache, nausea and application-site irritation. All drug-related AEs were mild, and no serious AEs were reported.
  
  
  CONCLUSIONS
  EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated.
authors: Clinical Research Center, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507-1912, USA. archerdf@evms.edu
authors: David F
authors: DF
authors: Archer
authors: Frank Z
authors: FZ
authors: Stanczyk
authors: Arkady
authors: A
authors: Rubin
authors: Marie
authors: M
authors: Foegh
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D003271:Contraceptive Agents, Female; D004997:Ethinyl Estradiol; D016912:Levonorgestrel