title: Dolutegravir Has No Effect on the Pharmacokinetics of Oral Contraceptives With Norgestimate and Ethinyl Estradiol.
abstract: BACKGROUND
  Dolutegravir (DTG; Tivicay; ViiV Healthcare, Research Triangle Park, NC) is an HIV-1-unboosted integrase inhibitor with no cytochrome P450 or uridine 5'diphosphate-glucuronosyltransferase inhibition or induction. As DTG is administered to HIV-1-infected women receiving oral contraceptives, assessing the potential for drug interactions was warranted.
  
  
  OBJECTIVE
  To determine the impact of DTG on the pharmacokinetics (PK) and pharmacodynamics (PD) of a common oral contraceptive, norgestimate/ethinyl estradiol (NGM/EE; Ortho-Cyclen; Ortho-McNeil-Janssen Pharmaceuticals, Inc, Raritan, NJ).
  
  
  METHODS
  This randomized, 2-period, double-blind, placebo-controlled study was conducted within 1 menstrual cycle at 1 clinical center in the United States; 16 women were enrolled. Participants received NGM 0.25 mg/EE 0.035 mg throughout the study. During days 1 to 10, they were randomized to receive twice-daily DTG 50 mg or matching placebo with food and switched to the other treatment during days 12 to 21.
  
  
  RESULTS
  Ratios of area under the concentration-time curve from time 0 until end of the dosage interval (AUC0-τ), maximum plasma concentration, and concentration at the end of the dosage interval of norelgestromin with DTG treatment to the same PK parameters with placebo treatment were 0.975, 0.890, and 0.932, respectively; for EE, ratios were 1.03, 0.99, and 1.02, respectively. No significant differences in luteinizing hormone, follicle-stimulating hormone, and progesterone were detected on days 1, 10, 11, 21, and 22. DTG steady-state AUC0-τ was similar to historical data. No severe or grade 3/4 adverse events occurred.
  
  
  CONCLUSIONS
  DTG had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without dose adjustment.
authors: GlaxoSmithKline, Research Triangle Park, NC, USA ivy.h.song@gsk.com.
authors: Ivy H
authors: IH
authors: Song
authors: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors: Julie
authors: J
authors: Borland
authors: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors: Shuguang
authors: S
authors: Chen
authors: Shionogi & Co, Ltd, Osaka, Japan.
authors: Toshihiro
authors: T
authors: Wajima
authors: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors: Amanda F
authors: AF
authors: Peppercorn
authors: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors: Stephen C
authors: SC
authors: Piscitelli
mesh_terms: D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004338:Drug Combinations; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010078:Oxazines; D010091:Oximes / Q000097:blood; D010879:Piperazines; D011374:Progesterone / Q000097:blood; D011728:Pyridones; D000099226:Dolutegravir
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D004997:Ethinyl Estradiol; D005640:Follicle Stimulating Hormone; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D007986:Luteinizing Hormone; D009644:Norgestrel; D010078:Oxazines; D010091:Oximes; D010879:Piperazines; D011374:Progesterone; D011728:Pyridones; D000099226:Dolutegravir; C109079:norgestimate, ethinyl estradiol drug combination; C449219:norelgestromin
keywords: HIV; drug interaction; healthy subjects; integrase inhibitor; pharmacokinetics