title: Pharmacokinetics of Once Versus Twice Daily Darunavir in Pregnant HIV-Infected Women.
abstract: OBJECTIVE
  To describe darunavir (DRV) pharmacokinetics with once-and twice-daily dosing during pregnancy and postpartum in HIV-infected women.
  
  
  METHODS
  Women were enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials Network Protocol P1026s, a prospective nonblinded study of antiretroviral pharmacokinetics in HIV-infected pregnant women that included separate cohorts receiving DRV/ritonavir dosed at either 800 mg/100 mg once daily or 600 mg/100 mg twice daily.
  
  
  METHODS
  Intensive steady-state 12- or 24-hour pharmacokinetic profiles were performed during the second trimester, third trimester, and postpartum. DRV was measured using high-performance liquid chromatography (detection limit: 0.09 μg/mL).
  
  
  RESULTS
  Pharmacokinetic data were available for 64 women (30 once daily and 34 twice daily dosing). Median DRV area under the concentration-time curve (AUC) and maximum concentration were significantly reduced during pregnancy with both dosing regimens compared with postpartum, whereas the last measurable concentration (Clast) was also reduced during pregnancy with once daily DRV. DRV AUC with once daily dosing was reduced by 38% during the second trimester and by 39% during the third trimester. With twice daily dosing, DRV AUC was reduced by 26% in both trimesters. The median (range) ratio of cord blood/maternal delivery DRV concentration in 32 paired samples was 0.18 (range: 0-0.82).
  
  
  CONCLUSIONS
  DRV exposure is reduced by pregnancy. To achieve DRV plasma concentrations during pregnancy equivalent to those seen in nonpregnant adults, an increased twice daily dose may be necessary. This may be especially important for treatment-experienced women who may have developed antiretroviral resistance mutations.
authors.affiliation: *Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Southern California School of Medicine, Los Angeles, CA; †Department of Biostatistics, Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA; ‡Department of Medicine, Children's Hospital Boston, Boston, MA; §HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; ‖Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand; ¶Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; #Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, MD; **National Institute of Allergy and Infectious Diseases, Bethesda, MD; and ††Department of Pediatrics, Boston University School of Medicine, Boston, MA.
authors.forename: Alice
authors.initials: A
authors.lastname: Stek
authors.forename: Brookie M
authors.initials: BM
authors.lastname: Best
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.forename: Edmund V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.forename: Regis
authors.initials: R
authors.lastname: Kreitchmann
authors.forename: Kittipong
authors.initials: K
authors.lastname: Rungruengthanakit
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Shapiro
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D000069454:Darunavir; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir