Substantial variation in transplacental transfer of chemotherapeutic agents in a mouse model.
OBJECTIVE
Data on the transplacental transfer of chemotherapeutic agents are lacking. We aimed to measure the maternofetal transfer of cytotoxic drugs in a mouse model.


METHODS
The transplacental transfer of doxorubicin (9 mg/kg), epirubicin (11 mg/kg), vinblastine (6 mg/kg), carboplatin (50 mg/kg), paclitaxel (10 mg/kg), and cytarabine (100 mg/kg) was tested in a C57/Bl6J mouse model. Ninety minutes after intravenous (IV) drug injection on gestational day 18.5, maternal and fetal blood were collected simultaneously. Plasma drug levels were determined using high performance liquid chromatography or atomic absorption spectrometry.


RESULTS
Fetal plasma concentrations of doxorubicin, epirubicin, vinblastine, and cytarabine were 5.1% ± 0.6% (n = 8), 4.8% ± 3.8% (n = 8), 13.8% ± 5.8% (n = 6), and 56.7% ± 22.6% (n = 6) of the maternal concentrations, respectively. Total platinum passed the mouse placenta easily (117.0% ± 38.9%, n = 6). Paclitaxel could not be detected in fetal plasma samples (n = 6).


CONCLUSIONS
Substantial variations in transplacental transfer were noted among the tested drugs. Current findings contribute to the understanding of reported pregnancy outcomes in humans.
Van Calsteren
Kristel
K
Department of Obstetrics and Gynecology, Division Gynecologic Oncology and Experimental Laboratory of Gynecology, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Belgium.
Verbesselt
Rene
R
Van Bree
Rieta
R
Heyns
Liesbeth
L
de Bruijn
Ernst
E
de Hoon
Jan
J
Amant
Frédéric
F
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000097:blood / Q000493:pharmacokinetics; D003561:Cytarabine / Q000097:blood / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000097:blood / Q000493:pharmacokinetics; D015251:Epirubicin / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005865:Gestational Age; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D014747:Vinblastine / Q000097:blood / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D003561:Cytarabine; D015251:Epirubicin; D014747:Vinblastine; D004317:Doxorubicin; D016190:Carboplatin; D017239:Paclitaxel