title: Pharmacokinetics and adhesion of the Agile transdermal contraceptive patch (AG200-15) during daily exposure to external conditions of heat, humidity and exercise.
abstract: BACKGROUND
  This study compares the pharmacokinetic profile, adhesion and safety of the AG200-15 Agile Patch (AP), a novel contraceptive patch releasing low-dose ethinyl estradiol (EE) and levonorgestrel (LNG), during wear under external conditions of heat, humidity and exercise versus normal activities.
  
  
  METHODS
  This open-label, three-period, five-treatment, crossover study randomized 24 healthy women to one of six external condition sequences. Each sequence included one normal wear and two external conditions periods. Participants wore the AP for 7 days under normal conditions or conditions of daily sauna, treadmill, whirlpool or cool water immersion, with a 7-day washout between treatments. Blood samples were collected for pharmacokinetic evaluations.
  
  
  RESULTS
  Twenty-four subjects completed the study. For EE, the mean maximum concentration level (Cmax), area under the plasma concentration-time curve from time 0 to 168 h (AUC(0-168)) and area under the plasma concentration-time curve from time 0 to infinity (AUC(0-inf)) were higher during normal conditions compared with all external conditions (geometric means ratio range: 80%-93%), except cool water. Mean steady-state concentrations (C(ss)) of EE were highest under normal conditions, followed by cool water, sauna, whirlpool and treadmill. The LNG mean C(max), AUC(0-168), AUC(0-inf) and C(ss) were higher under normal wear versus all other conditions (geometric means ratios: 75%-82%), with the exception of AUC(0-168), AUC(0-inf) and C(ss) for cold water. Median times to maximum concentration (Tmax) for EE and LNG were comparable across conditions. Patch adhesion was excellent under all conditions. Adverse events were mild, with none serious or leading to discontinuation.
  
  
  CONCLUSIONS
  Although slightly lower mean drug concentration levels were observed for whirlpool, treadmill and sauna, drug concentrations under all conditions were well within therapeutic ranges established for the AP during normal wear and within ranges reported for low-dose combination oral contraceptives. Patch adhesion was excellent; the AP was safe and well tolerated under all conditions.
authors.affiliation: Clinical Research Center, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507-1912, USA. archerdf@evms.edu
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Arkady
authors.initials: A
authors.lastname: Rubin
authors.forename: Marie
authors.initials: M
authors.lastname: Foegh
mesh_terms: D000269:Adhesives; D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004868:Equipment Failure; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015444:Exercise; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D007101:Immersion; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008875:Middle Aged; D057968:Transdermal Patch; D014867:Water
chemical_list: D000269:Adhesives; D003277:Contraceptives, Oral, Combined; D014867:Water; D004997:Ethinyl Estradiol; D016912:Levonorgestrel