title: Placental transfer of enfuvirtide in the ex vivo human placenta perfusion model.
abstract: OBJECTIVE
  The objective of the study was to determine the placental transfer of the antiretroviral fusion inhibitor, enfuvirtide (Fuzeon).
  
  
  METHODS
  Human cotyledons were perfused for 90 minutes in an open dual circuit with enfuvirtide, and fetal venous samples were collected every 5 minutes. Three perfusion experiments were validated using antipyrine.
  
  
  RESULTS
  Enfuvirtide was not detected in the fetal compartment in any of the 3 experiments. The mean concentration of the drug measured in the maternal compartment was 12,400 ng/mL (range, 6500-16,200 ng/mL), which is 2.5 times the maximum concentration recommended for patients treated with enfuvirtide.
  
  
  CONCLUSIONS
  Even at maternal concentrations twice above therapeutic levels, no placental transfer of enfuvirtide was observed. The high molecular weight of the molecule (4492 kDa) and its ionized state may account for the lack of placental transfer. This result suggests that enfuvirtide could be used in HIV-infected pregnant women without causing fetal exposure.
authors.affiliation: Department of Obstetrics and Gynecology, Louis Mourier Hospital, Assistance Publique-Hôpitaux de Paris, and Paris 7-Denis Diderot University, Paris, France.
authors.forename: Pierre-Francois
authors.initials: PF
authors.lastname: Ceccaldi
authors.forename: Claudia
authors.initials: C
authors.lastname: Ferreira
authors.forename: Laurent
authors.initials: L
authors.lastname: Gavard
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
mesh_terms: D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000493:pharmacokinetics* / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D010446:Peptide Fragments / Q000493:pharmacokinetics* / Q000494:pharmacology; D010920:Placenta / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy
chemical_list: D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide