title: Pharmacokinetics of tenofovir during pregnancy and postpartum.
abstract: OBJECTIVE
  Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum.
  
  
  METHODS
  International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300 mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24 h post dose (AUC) was ≥ 1.99 μg h/mL (nonpregnant historical control 10th percentile).
  
  
  RESULTS
  The median tenofovir AUC was decreased during the second (1.9 μg h/mL) and third (2.4 μg h/mL; P = 0.005) trimesters versus postpartum (3.0 μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P > 0.05). Median second/third-trimester troughs were lower (39/54 ng/mL) than postpartum (61 ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2 kg, respectively; P = 0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected.
  
  
  CONCLUSIONS
  This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (> 90 kg) or inadequate HIV RNA response.
authors.affiliation: School of Medicine-Rady Children's Hospital and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Best
authors.affiliation: Harvard Medical School, Children's Hospital Boston, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Burchett
authors.affiliation: Department of Preventive Medicine, Rush University Medical Center, Chicago, IL, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Stek
authors.affiliation: Division of Epidemiology and Biostatistics, University of Arizona Mel & Enid Zuckerman College of Public Health, Tucson, AZ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.affiliation: Harvard School of Public Health, Center for Biostatistics in AIDS Research, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Social and Scientific Systems, Silver Springs, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hawkins
authors.affiliation: Frontier Science & Technology Research Foundation, Amherst, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Byroads
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), Bethesda, MD, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Watts
authors.affiliation: National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Fletcher
authors.affiliation: School of Medicine-Rady Children's Hospital and Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA.
authors.forename: E V
authors.initials: EV
authors.lastname: Capparelli
authors.affiliation: Boston University School of Medicine, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D008297:Male; D049590:Postpartum Period; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D000068698:Tenofovir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D000068698:Tenofovir
keywords: HIV; antiretrovirals; pregnancy; prevention of perinatal transmission; tenofovir