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. STUDY DESIGN: 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.
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. STUDY DESIGN: 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.
Authors: Teska Schuurman; Ji-Ying Song; Vera Wolters; Marieke van de Ven; Nienke van Trommel; Ina Beerendonk; Frédéric Amant; Christianne Lok Journal: Arch Gynecol Obstet Date: 2022-09-27 Impact factor: 2.493