title: The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women.
abstract: BACKGROUND
  Coadministration of oral contraceptives with protease inhibitors is complicated by drug interactions. An open-label three-period single-sequence study assessed the effect of coadministration of atazanavir (ATV)/ritonavir (RTV) with Ortho Tri-Cyclen(®) and with Ortho Tri-Cyclen(®) LO (Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ, USA) on the pharmacokinetics (PK) of ethinyl estradiol (EE), norgestimate (NGM), ATV and RTV.
  
  
  METHODS
  A total of 20 healthy women aged 18-45 years received study treatments. In the lead-in period and in period 1, participants received a full cycle of Ortho Tri-Cyclen (EE 35 μg with NGM 0.18/0.215/0.25 mg) from days 1-28. In period 2, participants received a full cycle of Ortho Tri-Cyclen LO (EE 25 μg with NGM 0.18/0.215/0.25 mg) plus ATV/RTV (300/100 mg once daily) on days 29-42. PK assessments were performed on days 14 and 42 in periods 1 and 2, respectively.
  
  
  RESULTS
  ATV/RTV with dose-normalized EE/NGM resulted in geometric mean reductions of 16% in EE peak plasma concentration (C(max)), 19% in EE area under the concentration-time curve for a dosing interval (AUC([τ])) and 37% in EE lowest plasma concentration (C(min)), compared with EE 35 μg with NGM in the absence of ATV/RTV. NGM with EE and ATV/RTV 300/100 mg once daily resulted in increases of approximately 68%, 85% and 102% in 17-deacetyl NGM C(max), AUC((τ)) and C(min), respectively. Two participants discontinued the study because of adverse events.
  
  
  CONCLUSIONS
  ATV/RTV with Ortho Tri-Cyclen was well-tolerated and reductions in EE were not predicted to decrease contraceptive efficacy if the formulation contained ≥30 μg of EE.
authors: Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA. jenny.zhang1@bms.com
authors: Jenny
authors: J
authors: Zhang
authors: Ellen
authors: E
authors: Chung
authors: Cynthia
authors: C
authors: Yones
authors: Anna
authors: A
authors: Persson
authors: Lisa
authors: L
authors: Mahnke
authors: Timothy
authors: T
authors: Eley
authors: Xiaohui
authors: X
authors: Xu
authors: Richard
authors: R
authors: Bertz
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016387:Women's Health; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D009842:Oligopeptides; D011725:Pyridines; C109079:norgestimate, ethinyl estradiol drug combination; D009644:Norgestrel; D004997:Ethinyl Estradiol; D000069446:Atazanavir Sulfate; C017576:norgestimate; D019438:Ritonavir