title: Pharmacokinetics of Total and Unbound Etravirine in HIV-1-Infected Pregnant Women.
abstract: Treatment of HIV-1-infected women during pregnancy protects maternal health and reduces the risk of perinatal transmission of HIV-1. However, physiologic changes that occur during pregnancy may affect drug pharmacokinetics. This phase IIIb, open-label study evaluated the effects of pregnancy on the pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor etravirine.
  
  
  
  Eligible HIV-1-infected pregnant women (18-26 weeks gestation) on an individualized, highly active antiretroviral therapy regimen including etravirine 200 mg twice daily were enrolled. Blood samples to assess the pharmacokinetics of total and unbound etravirine were obtained at clinic visits during the second and third trimesters (24- to 28-weeks and 34- to 38-weeks gestation, respectively) and 6-12 weeks postpartum. At each time point, plasma concentrations were measured over 12 hours (12-hour time point was obtained before the second daily dose of etravirine); pharmacokinetic parameters were derived using noncompartmental analysis and were compared between pregnancy and postpartum using general linear models. Antiviral and immunologic response and safety were assessed at each visit.
  
  
  
  Etravirine pharmacokinetic profiles were available for 13 of 15 enrolled women. Exposure to total etravirine was generally higher during pregnancy compared with 6-12 weeks postpartum (1.2- to 1.4-fold); the differences were less pronounced for unbound (pharmacodynamically active) etravirine. Virologic response was generally preserved throughout the study, and no perinatal transmission was observed. Etravirine was generally safe and well tolerated.
  
  
  
  Etravirine 200 mg twice daily, as part of individualized combination antiretroviral therapy, may be a treatment option for HIV-1-infected pregnant women.
authors.affiliation: *Midway Immunology and Research Center, Fort Pierce, FL; †Triple O Research Institute PA, West Palm Beach, FL; ‡University of Puerto Rico School of Medicine, San Juan, PR; §Janssen Research & Development, Beerse, Belgium; and ‖Janssen Research & Development, Titusville, NJ.
authors.forename: Moti
authors.initials: M
authors.lastname: Ramgopal
authors.forename: Olayemi
authors.initials: O
authors.lastname: Osiyemi
authors.forename: Carmen
authors.initials: C
authors.lastname: Zorrilla
authors.forename: Herta M
authors.initials: HM
authors.lastname: Crauwels
authors.forename: Robert
authors.initials: R
authors.lastname: Ryan
authors.forename: Kimberley
authors.initials: K
authors.lastname: Brown
authors.forename: Vera
authors.initials: V
authors.lastname: Hillewaert
authors.forename: Bryan
authors.initials: B
authors.lastname: Baugh
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000635:transmission; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D009570:Nitriles; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism*; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011724:Pyridazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011743:Pyrimidines; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine