title: Contraceptive efficacy of oral and transdermal hormones when co-administered with protease inhibitors in HIV-1-infected women: pharmacokinetic results of ACTG trial A5188.
abstract: BACKGROUND
  Pharmacokinetic (PK) interactions between lopinavir/ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown.
  
  
  METHODS
  Using a standard noncompartmental PK analysis, we compared EE area under the time-concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1-infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration.
  
  
  RESULTS
  Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC0-168 h was 45% lower at 6010.36 pg·h·mL in those on LPV/r versus 10911.42 pg·h·mL in those on no HAART (P = 0.064). Pill EE median AUC0-48 hours was similarly 55% lower at 344.67 pg·h·mL in those on LPV/r versus 765.38 pg·h·mL in those on no HAART (P = 0.003). Patch NGMN AUC0-168 h however, was 138.39 ng·h·mL, 83% higher in the LPV/r group compared with the control AUC of 75.63 ng·h·mL (P = 0.036). After 3 weeks on the patch, LPV AUC0-8 h decreased by 19%, (P = 0.156).
  
  
  CONCLUSIONS
  Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Weill Cornell College of Medicine, New York, NY 10011, USA. mav9046@med.cornell.edu
authors.forename: Mary A
authors.initials: MA
authors.lastname: Vogler
authors.forename: Kristine
authors.initials: K
authors.lastname: Patterson
authors.forename: Lori
authors.initials: L
authors.lastname: Kamemoto
authors.forename: Jeong-Gun
authors.initials: JG
authors.lastname: Park
authors.forename: Heather
authors.initials: H
authors.lastname: Watts
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Susan E
authors.initials: SE
authors.lastname: Cohn
mesh_terms: D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D004967:Estrogens / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D061466:Lopinavir; D008875:Middle Aged; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010091:Oximes / Q000008:administration & dosage / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D057968:Transdermal Patch; D014481:United States
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D004967:Estrogens; D017320:HIV Protease Inhibitors; D010091:Oximes; D011744:Pyrimidinones; D061466:Lopinavir; D009644:Norgestrel; D004997:Ethinyl Estradiol; D019438:Ritonavir; C449219:norelgestromin