Maternofetal pharmacokinetics of a gadolinium chelate contrast agent in mice.
OBJECTIVE
To determine the maternofetal pharmacokinetics of gadoterate meglumine in mice during the first 48 hours following maternal intravenous injection of a high dose of 0.5 mmol of gadolinium per kilogram.


METHODS
All the studies complied with French law and the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Balb/C mice (n = 23) at 16 days of gestation were examined for 48 hours after maternal intravenous administration of 0.5 mmol gadolinium per kilogram of gadoterate meglumine. Gadolinium concentration in the placentas, fetuses, and amniotic fluid was determined by using mass spectrometry, and the total placental and fetal gadolinium content was calculated. Gadoterate meglumine half-life in the different compartments was estimated with one- and two-compartment models. Kruskal-Wallis and Wilcoxon signed-rank tests were used to compare the pharmacokinetic profiles.


RESULTS
Gadoterate meglumine passed the placental barrier, entering the fetuses and amniotic fluid before being redistributed back to the mother. The placental gadolinium concentration showed two-compartmental decay, with a first half-life of distribution of 47 minutes and a second half-life of elimination of 107 hours. The half-lives in the fetuses and amniotic fluid were, respectively, 4 and 5 hours and followed a monocompartmental model after the initial peak. The maximal gadolinium fetal concentration (31.8 nmol/g) was observed 30 minutes after injection, which corresponded to a total fetal content of 0.077% of the injected dose.


CONCLUSIONS
In mice, gadoterate meglumine, an extracellular nonspecific gadolinium chelate contrast medium, passed the placenta before being redistributed back to the mother, resulting in undetectable fetal concentrations after 48 hours.
INSERM, U970, Paris Cardiovascular Research Center-PARCC, Paris, France. olivier.clement@inserm.fr
Matthias R
MR
Mühler
Olivier
O
Clément
Laurent J
LJ
Salomon
Daniel
D
Balvay
Gwennhael
G
Autret
Catherine
C
Vayssettes
Charles A
CA
Cuénod
Nathalie
N
Siauve
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D008431:Maternal-Fetal Exchange; D008536:Meglumine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011247:Pregnancy; D018709:Statistics, Nonparametric
D003287:Contrast Media; D009942:Organometallic Compounds; D008536:Meglumine; C072417:gadoterate meglumine