Utilization of an ex vivo human placental perfusion model to predict potential fetal exposure to carboplatin during pregnancy

American Journal of Obstetrics and Gynecology
Judith A SmithJerrie S Refuerzo

Abstract

The objective of this study was to determine the fetal drug compartment concentrations when various concentrations of carboplatin cross the placental-trophoblastic barrier and the effect on the fetal kidneys. An ex vivo human placenta perfusion model was utilized. Term human placentae (n = 9) were collected immediately after delivery and then reperfused with plasma concentrations achieved with carboplatin an area under the curve of 5 (1000 ng/mL), 7.5 (5000 ng/mL), or 11 (11,000 ng/mL). Antipyrine was used as a reference compound. Samples were collected over 2 hours. Placental transfer was evaluated by computation of transport fraction and clearance index. Primary cells isolated by explant culture of 16-18 week old fetal organ tissues were incubated with carboplatin for up to 48 hours with untreated cell as controls. Immunohistochemical, flow cytometry analysis, and immunoblotting were applied for the expression of apoptosis-related proteins. Mean transport fractions for carboplatin at low, middle, and high concentrations were 0.05 ± 0.02, 0.04 ± 0.01, and 0.10 ± 0.01, respectively, with clearance indexes of 0.22 ± 0.01, 0.14 ± 0.08, and 0.50 ± 0.07, respectively. The fetal peak concentrations of carboplatin achieved were 61 ± ...Continue Reading

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Citations

Jun 16, 2015·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Ji Soo LeeDongeun Huh
Nov 11, 2014·Expert Opinion on Drug Safety·Tineke VandenbrouckeFrédéric Amant
Oct 4, 2015·American Journal of Obstetrics and Gynecology·Shari E GelberFrank A Chervenak
Jul 18, 2016·Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons·James MurphyBrent B Ward
Sep 10, 2011·Reproductive Toxicology·J R HutsonG Koren
May 12, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yong-Hong ZhangShu-Shen Liu
Jan 9, 2018·Expert Review of Clinical Pharmacology·Gideon Koren, Asher Ornoy
Sep 6, 2019·Interface Focus·Rajeendra L PemathilakaNicole N Hashemi
Jun 20, 2017·BioMed Research International·Nabil AbdallaWłodzimierz Sawicki
Apr 19, 2019·Scientific Reports·Hassan MelhemChristiane Albrecht

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