title: Maternal and fetal zidovudine pharmacokinetics during pregnancy and labour: too high dose infused at labour?
abstract: OBJECTIVE
  The main goal of the study was to describe the pharmacokinetics of maternal zidovudine (ZDV) administration during pregnancy and labour and to evaluate their impact on fetal concentrations and exposures.
  
  
  METHODS
  A total of 195 HIV-infected pregnant and non-pregnant women aged 16-59 years were included and 273 maternal and 79 cord blood ZDV concentrations were collected. A population pharmacokinetic model was developed to describe ZDV concentrations as a function of time in the mother and the fetus. Fetal exposures resulting from maternal oral administration and infusion were estimated and compared with therapeutic exposures (3-5 mg l(-1)  h) and to exposure providing higher risk of toxicity (>8.4 mg l(-1)  h). Different protocols for ZDV administration during labour were simulated.
  
  
  RESULTS
  The median fetal exposure and the percentage of children with values above 8.4 mg l(-1)  h were 3.20 mg l(-1)  h and 0% after maternal oral administration, respectively, and 9.71 mg l(-1)  h and 51% after maternal infusion during labour. Two options were considered to reduce fetal exposure during labour: (i) maternal infusion rates could be 1 mg kg(-1)  h(-1) during 1 h followed by 0.5 mg kg(-1)  h(-1) and (ii) the mother could only take oral ZDV every 5 h from start of labour until delivery with her neonate having their first ZDV dose as soon as possible after birth.
  
  
  CONCLUSIONS
  Zidovudine exposures are very important during labour and during the first days of a neonate's life. Maternal ZDV dose should be reduced in addition to the neonate doses reduction already proposed.
authors.affiliation: EA 3620 Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Unité de Recherche Clinique, AP-HP, Hôpital Tarnier, Paris, France.
authors.forename: Floris
authors.initials: F
authors.lastname: Fauchet
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
authors.forename: Elodie
authors.initials: E
authors.lastname: Valade
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Pannier
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Firtion
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Naim
authors.initials: N
authors.lastname: Bouazza
authors.forename: Saik
authors.initials: S
authors.lastname: Urien
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007743:Labor, Obstetric / Q000378:metabolism*; D008875:Middle Aged; D011247:Pregnancy / Q000378:metabolism*; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D015215:Zidovudine
keywords: HIV; intrapartum; population pharmacokinetics; prevention of mother to child transmission; zidovudine