title: Effect of the coadministration of daclatasvir on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate.
abstract: BACKGROUND
  Daclatasvir is a highly selective NS5A replication complex inhibitor currently in development for the treatment of chronic hepatitis C infection. Daclatasvir is active at picomolar concentrations and demonstrates in vitro activity against a broad range of HCV genotypes. The primary objective of this study was to assess the effect of daclatasvir on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate (Ortho Tri-Cyclen(®)).
  
  
  METHODS
  In this open-label single-sequence study, 20 healthy female subjects received ethinyl estradiol and norgestimate for three cycles, with coadministration of daclatasvir in cycle 3. Pharmacokinetics of ethinyl estradiol and the active metabolites of norgestimate (norelgestromin and norgestrel) were assessed in cycles 2 and 3.
  
  
  RESULTS
  Adjusted ratios of geometric means and 90% CIs were estimated for the maximum observed plasma concentration (ethinyl estradiol 1.11 [1.02, 1.20], norelgestromin 1.06 [0.99, 1.14] and norgestrel 1.07 [0.99, 1.16]) and area under the plasma concentration-time curve in one dosing interval (ethinyl estradiol 1.01 [0.95, 1.07], norelgestromin 1.12 [1.06, 1.17] and norgestrel 1.12 [1.02, 1.23]).
  
  
  CONCLUSIONS
  Coadministration of daclatasvir resulted in no clinically relevant effects on exposure to ethinyl estradiol, norelgestromin or norgestrel.
authors.affiliation: Research and Development, Bristol-Myers Squibb, Hopewell, NJ, USA. marc.bifano@bms.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Bifano
authors.forename: Heather
authors.initials: H
authors.lastname: Sevinsky
authors.forename: Carey
authors.initials: C
authors.lastname: Hwang
authors.forename: Hamza
authors.initials: H
authors.lastname: Kandoussi
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Dennis
authors.initials: D
authors.lastname: Grasela
authors.forename: Richard
authors.initials: R
authors.lastname: Bertz
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D016903:Drug Monitoring; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D009644:Norgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011759:Pyrrolidines; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D007093:Imidazoles; D011759:Pyrrolidines; C109079:norgestimate, ethinyl estradiol drug combination; D009644:Norgestrel; D004997:Ethinyl Estradiol; D014633:Valine; C549273:daclatasvir