Comparative transplacental transfer of taxanes using the human perfused cotyledon placental model - 21/11/12

Doi : 10.1016/j.ajog.2012.10.007

Paul Berveiller, MD ^a,^b,^c,^⁎ , Cécile Vinot, MSc ^a, Olivier Mir, MD ^c,^d, Sophie Broutin, PhD, PharmD ^e, Alain Deroussent, MSc ^f, Atmane Seck, MSc ^e,^f, Sandra Camps, PharmD ^g, Angelo Paci, PhD, PharmD ^e,^f, Sophie Gil, PhD ^b, Jean-Marc Tréluyer, MD, PhD ^a,^c
^a Department of Clinical Pharmacology and Clinical Research Unit, Institut National de la Santé et de la Recherche Médicale Centre d'Investigations Cliniques P 0901, Cochin Teaching Hospital, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
^b Institut National de la Santé et de la Recherche Médicale Unit 767–PremUp Foundation, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
^c French Network Cancers Associés à La Grossesse, Paris, France
^d Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
^e Department of Pharmacology and Drug Analysis, Institut Gustave Roussy, Villejuif, France
^f Centre National de la Recherche Scientifique Research Unit 8203, Université Paris-Sud, Institut Gustave Roussy, Villejuif, France
^g Department of Pharmacy, Institut Mutualiste Montsouris, Paris, France

Reprints: Paul Berveiller, MD, PhD, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherches-S 767–PremUp Foundation, Pharmaceutical and Biological Sciences Faculty–Université Paris Descartes, Sorbonne Paris Cité–4, Avenue de l'Observatoire, F75006 Paris, France

Résumé

Objectives

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.

Study Design

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.

Conclusion

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.

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Key words : cancer, docetaxel, paclitaxel, placenta, pregnancy, taxanes

Plan

Materials and Methods

Materials

Methods

Study of placental accumulation–quantitative analyze of taxanes

Data and statistical analysis

Results

Transplacental Transfer of Ap

Transplacental transfer of paclitaxel with 2 g/L and 30 g/L of albumin

Transplacental transfer of docetaxel with 2 g/L and 30 g/L of albumin

Placental uptake of taxanes

Comparative transplacental transfer of paclitaxel and docetaxel

Comment

Conclusion

	The last 2 authors contributed equally to this article.
	O.M. has acted as paid consultant for Roche, Servier, and Pfizer. No other author reports a conflict of interest.
	Supported by a study grant from the Institut National de la Santé et de la Recherche Médicale and the Association pour la Recherche contre le Cancer.
	Cite this article as: Berveiller P, Vinot C, Mir O, et al. Comparative transplacental transfer of taxanes using the human perfused cotyledon placental model. Am J Obstet Gynecol 2012;207:514.e1-7.