Document Detail


Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model.
MedLine Citation:
PMID:  20846713     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-17
Journal Detail:
Title:  Gynecologic oncology     Volume:  119     ISSN:  1095-6859     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-08     Completed Date:  2010-11-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  594-600     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Amniotic Fluid / 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:
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

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