| Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model. | |
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MedLine Citation:
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PMID: 20846713 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The paucity of data on the fetal effects of prenatal exposure to chemotherapy prompted us to study transplacental transport of chemotherapeutic agents. METHODS: Fluorouracil-epirubicin-cyclophosphamide (FEC) and doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD) were administered to pregnant baboons. At predefined time points over the first 25 h after drug administration, fetal and maternal blood samples, amniotic fluid (AF), urine, fetal and maternal tissues, and cerebrospinal fluid (CSF) were collected. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) were used for bioanalysis of doxorubicin, epirubicin, vinblastine, and cyclophosphamide. RESULTS: In nine baboons, at a median gestational age of 139 days (range, 93-169), FEC 100% (n = 2), FEC 200% (n=1), ABVD 100% (n = 5), and ABVD 200% (n = 1) were administered. The obtained ratios of fetal/maternal drug concentration in the different simultaneously collected samples were used as a measure for transplacental transfer. Fetal plasma concentrations of doxorubicin and epirubicin averaged 7.5 ± 3.2% (n = 6) and 4.0 ± 1.6% (n = 8) of maternal concentrations, respectively. Fetal tissues contained 6.3 ± 7.9% and 8.7 ± 8.1% of maternal tissue concentrations for doxorubicin and epirubicin, respectively. Vinblastine concentrations in fetal plasma averaged 18.5 ± 15.5% (n=9) of maternal concentrations. Anthracyclines and vinblastine were neither detectable in maternal nor in fetal brain/CSF. 4-Hydroxy-cyclophosphamide concentrations in fetal plasma and CSF averaged 25.1 ± 6.3% (n = 3) and 63.0% (n = 1) of the maternal concentrations, respectively. CONCLUSION: This study shows limited fetal exposure after maternal administration of doxorubicin, epirubicin, vinblastine, and 4-hydroxy-cyclophosphamide. |
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Authors:
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K Van Calsteren; R Verbesselt; J Beijnen; R Devlieger; L De Catte; D C Chai; R Van Bree; L Heyns; J de Hoon; F Amant |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-17 |
Journal Detail:
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Title: Gynecologic oncology Volume: 119 ISSN: 1095-6859 ISO Abbreviation: Gynecol. Oncol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-08 Completed Date: 2010-11-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0365304 Medline TA: Gynecol Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 594-600 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amniotic Fluid
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metabolism Animals Antineoplastic Combined Chemotherapy Protocols / blood, pharmacokinetics* Bleomycin / blood, pharmacokinetics Chromatography, High Pressure Liquid Cyclophosphamide / analogs & derivatives*, blood, pharmacokinetics Dacarbazine / blood, pharmacokinetics Doxorubicin / blood, pharmacokinetics Epirubicin / blood, pharmacokinetics Female Fetal Blood / metabolism* Fluorouracil / blood, pharmacokinetics Mass Spectrometry Papio Placenta / metabolism* Pregnancy Pregnancy, Animal / blood, metabolism* Vinblastine / blood, pharmacokinetics |
| Chemical | |
Reg. No./Substance:
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11056-06-7/Bleomycin; 23214-92-8/Doxorubicin; 40277-05-2/4-hydroxycyclophosphamide; 4342-03-4/Dacarbazine; 50-18-0/Cyclophosphamide; 51-21-8/Fluorouracil; 56420-45-2/Epirubicin; 865-21-4/Vinblastine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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