Substantial variation in transplacental transfer of chemotherapeutic agents in a mouse model

Reprod Sci. 2011 Jan;18(1):57-63. doi: 10.1177/1933719110379650. Epub 2010 Sep 8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Carboplatin / blood
  • Carboplatin / pharmacokinetics
  • Cytarabine / blood
  • Cytarabine / pharmacokinetics
  • Doxorubicin / blood
  • Doxorubicin / pharmacokinetics
  • Epirubicin / blood
  • Epirubicin / pharmacokinetics
  • Female
  • Fetal Blood / chemistry
  • Gestational Age
  • Injections, Intravenous
  • Maternal-Fetal Exchange*
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Paclitaxel / blood
  • Paclitaxel / pharmacokinetics
  • Placenta / metabolism
  • Pregnancy
  • Vinblastine / blood
  • Vinblastine / pharmacokinetics

Substances

  • Antineoplastic Agents
  • Cytarabine
  • Epirubicin
  • Vinblastine
  • Doxorubicin
  • Carboplatin
  • Paclitaxel