title: Pharmacokinetic modelling of the placental transfer of nelfinavir and its M8 metabolite: a population study using 75 maternal-cord plasma samples.
abstract: OBJECTIVE
  A population pharmacokinetic model was developed to characterize the transfer of nelfinavir and its active metabolite M8 from maternal to cord plasma and amniotic fluid.
  
  
  METHODS
  Concentration data were obtained from 75 women on the day of delivery and for whom maternal, umbilical plasma and amniotic fluid samples were collected. Data from 53 pregnant, 61 nonpregnant and seven consecutively pregnant and non pregnant women were then added to the database, the contents of which were analyzed using NONMEM.
  
  
  RESULTS
  Nelfinavir and M8 concentrations in maternal plasma, umbilical plasma and amniotic fluid were described by six connected compartments. Mean (% intersubject variability) population estimates were: absorption rate 00.67 h(-1), lag time 00.87 h, oral clearance and volume of distribution: 39.5 l h(-1) (53%), and 557 l for non pregnant and pregnant women, respectively, and 115 l h(-1) (132%) and 1626 l, respectively, on the day of delivery, M8 formation clearance 0.77 l h(-1) and M8 elimination rate constant 03.41 h(-1) (74%). For nelfinavir and M8, respectively, the mother-to-cord parameters were 0.058 l h(-1) (34%), and 00.35 h(-1) (76%), the cord-to-amniotic fluid rate constants were 0.23 and 00.59 h(-1), and the elimination rate constants from amniotic fluid were 0.36 and 00.49 h(-1). The nelfinavir fetus : maternal concentration ratio was 25% for maternal concentrations between 0.1 and 2.5 mg l(-1), between the 31 and 41st week of gestation.
  
  
  CONCLUSIONS
  The low transfer of nelfinavir from the placenta is unlikely to protect the fetus from vertical HIV-1 transmission.
authors: Pharmacologie Clinique, Assistance publique- Hôpitaux de Paris, groupe hospitalier Cochin-Saint-Vincent-de-Paul, Faculté de médecine René Descartes, Université Paris 5, Paris, France. deborah.hirt@univ-paris5.fr
authors: Déborah
authors: D
authors: Hirt
authors: Saïk
authors: S
authors: Urien
authors: Vincent
authors: V
authors: Jullien
authors: Ghislaine
authors: G
authors: Firtion
authors: Hélène
authors: H
authors: Chappuy
authors: Elisabeth
authors: E
authors: Rey
authors: Gérard
authors: G
authors: Pons
authors: Laurent
authors: L
authors: Mandelbrot
authors: Jean-Marc
authors: JM
authors: Treluyer
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D019888:Nelfinavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D019888:Nelfinavir