Placental transfer and milk secretion of gadodiamide injection in rats.
The disposition of gadodiamide (CAS 122795-43-1) injection (Omniscan), a nonionic paramagnetic contrast-enhancing medium developed for magnetic resonance imaging, was characterized in the pregnant and lactating rat. After a single intravenous dose of 0.3 mmol/kg 14C-labeled gadodiamide to rats on day 18 of gestation, the maximum levels of radioactivity in the fetus were attained at 5 min, and were approximately 170 times lower than those in the maternal plasma. The AUC ratio of fetal to maternal blood was less than 0.1. Moreover, the distribution percentage 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 autoradiography showed that the smallest amounts of radioactivity were present in the fetus, whereas the highest concentrations of radioactivity were noted in the fetal membrane and the kidney at 24 h after dosing. These results indicate that exposure of the developing rat fetus to gadodiamide after maternal drug administration is quantitatively small. The radioactivity levels in the milk increased with time, reaching a maximum 1 h after dosing, and gradually decreased to levels below detection limits over 8 h. A comparison of the AUCs of milk and plasma showed the comparatively small amounts of the drug excreted into milk.
Okazaki
O
O
Developmental Research Laboratories, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Murayama
N
N
Masubuchi
N
N
Nomura
H
H
Hakusui
H
H
D000818:Animals; D001345:Autoradiography; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D019786:Gadolinium DTPA; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000378:metabolism*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D009942:Organometallic Compounds; D004369:Pentetic Acid; C064925:gadodiamide; D019786:Gadolinium DTPA