Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial

Contraception. 2012 Jun;85(6):595-601. doi: 10.1016/j.contraception.2011.10.006. Epub 2011 Nov 30.


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.

Study design: 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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Contraceptive Agents, Female / administration & dosage*
  • Cross-Over Studies
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / blood
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / blood
  • Levonorgestrel / pharmacokinetics*


  • Contraceptive Agents, Female
  • Ethinyl Estradiol
  • Levonorgestrel

Associated data