title: Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily.
abstract: OBJECTIVE
  Antiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission of HIV and for maternal care management. Physiological changes during pregnancy can affect pharmacokinetics, potentially altering pharmacological activity. We therefore evaluated the pharmacokinetics of twice-daily (bid) darunavir in HIV-1-infected pregnant women.
  
  
  METHODS
  HIV-1-infected pregnant women receiving an antiretroviral regimen containing darunavir/ritonavir 600/100 mg bid were enrolled in this study. Total and unbound darunavir and total ritonavir plasma concentrations were obtained over 12 h during the second and third trimesters and postpartum. Total darunavir and ritonavir plasma concentrations were determined using a validated high-performance liquid chromatography tandem mass spectrometry assay and unbound darunavir was determined using (14) C-darunavir-fortified plasma. Pharmacokinetic parameters were derived using noncompartmental analysis.
  
  
  RESULTS
  Data were available for 14 women. The area under the plasma concentration-time curve from 0 to 12 h (AUC12h) for total darunavir was 17-24% lower during pregnancy than postpartum. The AUC12h for unbound darunavir was minimally reduced during pregnancy vs. postpartum. The minimum plasma concentration (Cmin) of total and unbound darunavir was on average 43-86% and 10-14% higher, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 33% at baseline and increased to 73-90% during treatment; the percentage CD4 count increased over time. One serious adverse event was reported (increased transaminase). All 12 infants born to women remaining in the study at delivery were HIV-1-negative; four of these infants were premature.
  
  
  CONCLUSIONS
  Total darunavir exposure decreased during pregnancy. No clinically relevant change in unbound (active) darunavir occurred during pregnancy, suggesting that no dose adjustment is required for darunavir/ritonavir 600/100 mg bid in pregnant women.
authors.affiliation: University of Puerto Rico School of Medicine, San Juan, Puerto Rico.
authors.forename: C D
authors.initials: CD
authors.lastname: Zorrilla
authors.forename: R
authors.initials: R
authors.lastname: Wright
authors.forename: O O
authors.initials: OO
authors.lastname: Osiyemi
authors.forename: S
authors.initials: S
authors.lastname: Yasin
authors.forename: B
authors.initials: B
authors.lastname: Baugh
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Coate
authors.forename: P
authors.initials: P
authors.lastname: Verboven
authors.forename: J
authors.initials: J
authors.lastname: Mrus
authors.forename: R
authors.initials: R
authors.lastname: Falcon
authors.forename: T N
authors.initials: TN
authors.lastname: Kakuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000069454:Darunavir; D004334:Drug Administration Schedule; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000378:metabolism*; D011256:Pregnancy Outcome; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir
keywords: HIV; darunavir; pharmacokinetics; pregnancy; ritonavir