title: Therapeutically equivalent pharmacokinetic profile across three application sites for AG200-15, a novel low-estrogen dose contraceptive patch.
abstract: BACKGROUND
  AG200-15 Agile Patch (AP) is a novel 7-day contraceptive patch providing ethinyl estradiol (EE) exposure comparable to low-dose combination oral contraceptives. This study determined whether application of the AP to three different anatomical sites (lower abdomen, buttock and upper torso) influences the pharmacokinetic profile of EE and levonorgestrel (LNG).
  
  
  METHODS
  In this open-label, three-period, crossover study, 24 subjects were randomized to one of six treatment sequences; each included application of patch to abdomen, buttock and upper torso, with the AP worn on one site for 7 days. After a 7-day washout, a new patch was applied to the next anatomical site. Multiple blood samples were collected up to 240 h after patch application.
  
  
  RESULTS
  For plasma EE levels, median time to maximum drug concentration (Tmax, 24-48 h) and mean maximum concentration (Cmax, 47.9-61.5 pg/mL) were similar among application sites. Compared with lower abdomen, EE exposure was higher (16%-30%) at buttock and upper torso (15%-22%). For plasma LNG levels, median Tmax (72-120 h) and mean Cmax (1436-1589 pg/mL) were similar across application sites. Compared with lower abdomen, LNG exposure was higher at buttock (1%-7%) and upper torso (16%-17%). No serious adverse events (AEs) or AE-related discontinuations occurred. The most common treatment-emergent AEs were nausea, application site pruritus and headache, with frequencies comparable across anatomical sites.
  
  
  CONCLUSIONS
  Absorption from the abdomen was slightly lower versus other sites; however, exposure to EE and LNG for all sites was therapeutically equivalent. The AP was well tolerated at all three anatomical sites.
authors.affiliation: University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA. fstanczyk@socal.rr.com
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Arkady
authors.initials: A
authors.lastname: Rubin
authors.forename: Marie
authors.initials: M
authors.lastname: Foegh
mesh_terms: D000005:Abdomen; D000328:Adult; D002081:Buttocks; D015331:Cohort Studies; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D005260:Female; D006207:Half-Life; D006261:Headache / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D011537:Pruritus / Q000139:chemically induced / Q000453:epidemiology; D012869:Skin Absorption; D013909:Thorax; D057968:Transdermal Patch; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D004338:Drug Combinations; D004997:Ethinyl Estradiol; D016912:Levonorgestrel