PLACENTAL-TRANSFER AND MILK SECRETION OF GADODIAMIDE INJECTION IN RATS

The disposition of gadodiamide (CAS 122795-43-1) injection (Omniscan(R )), a nonionic paramagnetic contrast-enhancing medium developed for ma gnetic resonance imaging, was characterized in the pregnant and lactat ing rat. After a single intravenous dose of 0.3 mmol/kg C-14-labeled g adodiamide to rats on day 18 of gestation, the maximum levels of radio activity in the fetus were attained at 5 min, and were approximately 1 70 times lower than those in the maternal plasma. The AUC ratio of fet al to maternal blood was less than 0.1. Moreover, the distribution per centage of radioactivity in the fetus were on the average 0.01% of the administered dose up to 4 h, and trace amounts of radioactivity were present in fetal tissues at 24 h after dosing. Whole body autoradiogra phy showed that the smallest amounts of radioactivity were present in the fetus, whereas the highest concentrations of radioactivity were no ted in the fetal membrane and the kidney at 24 h after dosing. These r esults indicate that exposure of the developing rat fetus to gadodiami de after maternal drug administration is quantitatively small. The rad ioactivity levels in the milk increased with time, reaching a maximum 1 h after dosing, and gradually decreased to levels below detection li mits over 8 h. A comparison of the AUCs of milk and plasma showed the comparatively small amounts of the drug excreted into milk.