Transplacental transfer of anthracyclines, vinblastine, and 4-hydroxy-cyclophosphamide in a baboon model.
Gynecol Oncol
; 119(3): 594-600, 2010 Dec.
Article
in En
| MEDLINE
| ID: mdl-20846713
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Placenta
/
Pregnancy, Animal
/
Antineoplastic Combined Chemotherapy Protocols
/
Cyclophosphamide
/
Fetal Blood
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Gynecol Oncol
Year:
2010
Document type:
Article