title: Raltegravir pharmacokinetics during pregnancy.
abstract: OBJECTIVE
  We evaluated the pharmacokinetics (PK) of raltegravir in HIV-infected women during pregnancy and postpartum.
  
  
  METHODS
  International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is an ongoing prospective study of antiretroviral PK during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady-state 12-hour PK profiles performed during pregnancy and at 6- to 12-week postpartum. Targets were trough concentration above 0.035 μg/mL, the estimated 10th percentile in nonpregnant historical controls.
  
  
  RESULTS
  Median raltegravir area under the curve was 6.6 μg·h/mL for second trimester (n = 16), 5.4 μg·h/mL for third trimester (n = 41), and 11.6 μg·h/mL postpartum (n = 38) (P = 0.03 postpartum vs second trimester, P = 0.001 pp vs third trimester). Trough concentrations were above the target in 69%, 80%, and 79% of second trimester, third trimester, and postpartum subjects, respectively, with wide variability (<0.010-0.917 μg/mL), and no significant difference between third trimester and postpartum trough concentrations was detected. The median ratio of cord blood/maternal raltegravir concentrations was 1.5. HIV RNA levels were <400 copies per milliliter in 92% of women at delivery. Adverse events included elevated liver transaminases in 1 woman and vomiting in 1. All infants with known status are HIV uninfected.
  
  
  CONCLUSIONS
  Median raltegravir area under the curve was reduced by approximately 50% during pregnancy; trough concentrations were frequently below target both during late pregnancy and postpartum. Raltegravir readily crossed the placenta. High rates of viral suppression at delivery and the lack of a clear relationship between raltegravir concentration and virologic effect in nonpregnant adults suggest that despite the decreased exposure during pregnancy, a higher dose is not necessary.
authors.affiliation: *Office of the Global AIDS Coordinator, U.S. Department of State, Washington, DC; †Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, CA; ‡Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA; §Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‖Program for HIV Prevention and Treatment (IRD URI 174), Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ¶Department of Clinical Pharmacy, Drug Research Unit, University of California, San Francisco, San Francisco, CA; #HIV/AIDS Research Department, Irmandade da Santa Casa de Misericordia de Porto Alegre, Porto Alegre, Brazil; **Boston Children's Hospital, Harvard Medical School, Boston, MA; ††Social and Scientific Systems, Inc, Silver Spring, MD; ‡‡Maternal, Adolescent, and Pediatric Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD; and §§Department of Pediatrics, Boston University School of Medicine, Boston, MA.
authors.forename: D Heather
authors.initials: DH
authors.lastname: Watts
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: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Francesca
authors.initials: F
authors.lastname: Aweeka
authors.forename: Patty
authors.initials: P
authors.lastname: Lizak
authors.forename: Regis
authors.initials: R
authors.lastname: Kreitchmann
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.forename: David E
authors.initials: DE
authors.lastname: Shapiro
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hawkins
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.forename: Mark
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000328:Adult; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy / Q000378:metabolism; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D011264:Pregnancy Trimesters / Q000378:metabolism; D011760:Pyrrolidinones / Q000097:blood / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium