title: Comparative transplacental transfer of taxanes using the human perfused cotyledon placental model.
abstract: OBJECTIVE
  The use of taxanes (paclitaxel and docetaxel) in pregnant cancer patients is increasing. We aimed to compare their transplacental transfer using the gold standard human placental perfusion model, to guide drug selection.
  
  
  METHODS
  Term placentas were perfused with paclitaxel or docetaxel and 2 different albumin concentrations. Main transfer parameters such as fetal transfer rate (FTR), clearance index, and placental uptake of taxanes were assessed.
  
  
  RESULTS
  Twelve placentas were perfused, 6 with paclitaxel and 6 with docetaxel. Mean FTR of paclitaxel decreased significantly from 5.67 ± 0.02% in low albumin conditions to 1.72 ± 0.09% in physiological albumin conditions. Similarly, mean clearance index decreased significantly from 0.22 ± 0.02 to 0.09 ± 0.01. Regarding docetaxel, mean FTR were similar in low albumin and physiological conditions (5.03 ± 0.60% and 4.04 ± 0.22%, respectively) while mean clearance index decreased significantly from 0.18 ± 0.02 to 0.13 ± 0.01. Taxanes accumulation in cotyledon was similar for docetaxel and paclitaxel: 4.54 ± 1.84% vs 3.31 ± 1.88%, respectively.
  
  
  CONCLUSIONS
  Transplacental transfer and placental accumulation of paclitaxel and docetaxel were low and similar, especially in physiological conditions of albumin. Further studies are warranted to optimize the selection of a taxane in pregnant cancer patients.
authors.affiliation: Department of Clinical Pharmacology and Clinical Research Unit, INSERM Cliniques P 0901, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. paul.berveiller@inserm.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Berveiller
authors.forename: Cécile
authors.initials: C
authors.lastname: Vinot
authors.forename: Olivier
authors.initials: O
authors.lastname: Mir
authors.forename: Sophie
authors.initials: S
authors.lastname: Broutin
authors.forename: Alain
authors.initials: A
authors.lastname: Deroussent
authors.forename: Atmane
authors.initials: A
authors.lastname: Seck
authors.forename: Sandra
authors.initials: S
authors.lastname: Camps
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Sophie
authors.initials: S
authors.lastname: Gil
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D043823:Taxoids / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel